Shortly before Miller's death in late 1995, he had his agent contact author/editor Terry Bisson for help in finishing Saint Leibowitz and the Wild Horse Woman. Miller had finished the majority of the novel, but was suffering from a bad case of writer's block and wanted to ensure that his second novel would be finished. According to Bisson, all he did was go in and tie up the loose ends Miller had left. In truth, Bisson's hand is practically invisible.

The novel tells the story of Blacktooth St. George, a monk at the titular abbey about seventy years after the second section of A Canticle for Leibowitz. Unlike his predecessor, Brother Francis Gerard of Utah (from Canticle's first section), Blacktooth wants nothing more than to be released from his vows and the abbey to which he once fled as a refuge, but which he now sees as a prison. Father Jarad refuses to permit him to foreswear his vows, but eventually permits his leaving the abbey as Cardinal Brownpony's personal secretary.

The remainder of the novel looks at the political situation in the thirty-third century as papacy and empire clash in a struggle reminiscent of the twelfth century investiture controversy mixed with the Avignon captivity. Several popes die in rapid succession, giving Miller a chance to use his wry sense of humor about their deaths. Eventually, following an hilarious description of the conclave of Cardinals, Pope Amen Specklebird, a mystic/hermit/magician, is elected, precipitating a renewal of schism between the Church and empire.

Miller's world is far more complex than glimpsed in A Canticle for Leibowitz. He examines the cultures of the nomadic tribes which exist in the regions around the Christian states and the Empire of Texark. Much of the novel focuses on the war and alliances between the nomadic tribes, the Church and Texark. Always near center stage are Miller's characters Blacktooth, Cardinal Brownpony and a spook girl named drea, who has become Blacktooth's temptress and the primary cross he must bear.

As Blacktooth grows spiritually, he also grows as an individual, not only leaving the cloistered world of Saint Leibowitz Abbey and his job as Cardinal Brownpony's personal secretary, but also standing up to a wide variety of authority figures. Even as Blacktooth tries to put the clergy behind him, he rises in the estimation of many important Cardinals and the Church's own hierarchy. Miller's characterization of Blacktooth at the novel's beginning and Bisson's representation of him at the novel's end are as different as two characters can be. Nevertheless, each step from Brother Blacktooth to his final destination is well thought out and flows naturally, showing a true sense of character development.

Spirituality also continues to play a large role in the world of the Leibowitzian Order. Benjamin, the Wandering Jew of the original novel, returns, but in Saint Leibowitz and the Wild Horse Woman, he is joined by a visionary (Blacktooth), a healing/stigmata-riddled nun, and the holy hermit, Pope Amen Specklebird. Miller does not attempt to explain the magic surrounding these characters, which sets them apart from the magicians and mystics of the Nomad tribes. In the latter case, Miller leaves no doubt that the magic is caused by remnants of the Flame Deluge. In the case of the Christians' magic, he leaves open the possibility that they are showing the Hand of God in their abilities.

One of the rough spots of Saint Leibowitz and the Wild Horse Woman is the redundancy of his descriptions of events or objects, causing the reader to pause and think back to his earlier reference to the same item. Similarly, Miller includes a great deal of background information which could easily have been left out of the novel without damaging the plot or texture. In many cases, it may even have served to tighten the novel.

Another area of confusion is Miller's frequent use of multiple names to designate the same character. Blacktooth St. George is also referred to as Nimmy or Nyinden. Similarly, Nomadic characters are referred to by both their native names, their titles and English translations of their names. Although this is a realistic way of naming them, the reader does not always have a clear image of the individual being discussed.

Many of the characters Miller has created, however, are memorable. Pope Amen Specklebird and Wooshin rank with Brother Francis of Utah. Even the lesser individual characters, such as Filpeo Harq, the seventh Hannegan of Texark, ranks as a stronger character than Father Zerchi from the final section of A Canticle for Leibowitz. Finally, Miller and Bisson chose to leave the mystery surrounding Benjamin intact. The Old Jew is still going about muttering his unintelligible comments (to the other characters).

Saint Leibowitz and the Wild Horse Woman is not A Canticle for Leibowitz, nor should it be. It is, in fact, a much more ambitious novel than Miller's earlier output. Instead of being a series of novella-length stories tied together, Miller has turned out a novel longer than the earlier book. Rather than focusing on a small, self-contained area, Miller has set himself the task of exploring the world. In this he has grown, for the final section of A Canticle for Leibowitz, where Miller explored the world outside the Abbey for the first time, is the weakest portion of the earlier book. In Saint Leibowitz and the Wild Horse Woman, he may not always succeed, but he hits the target frequently enough to have written a very good novel.