Only three women characters of any consequence appear in Arrowsmith: Madeline Fox, Leora, and Joyce. Madeline and Joyce both reflect the characteristics of Lewis' first wife, Grace Hegger Lewis. Leora is probably modeled after Paul de Kruif's idea of his own wife, although a woman novelist, Edith Summers, claimed to be the original of Leora.
Dorothy Thompson considered Leora the most lifelike character in all the Lewis gallery, doubting if even her creator realized "how truly her life fulfills the longing of the real woman." When Leora's baby is born dead and she realizes that she can never have another, continues Miss Thompson, she does not despair but becomes more and more absorbed in her husband, not much caring whether she has children or not. Mark Schorer agrees with this estimate of Leora, considering her the most realized figure in all the novels. A few dissenters consider her lazy, careless, and slightly stupid. Yet she never missed a chance to aid her husband, whether by earning a living as a secretary, assisting him in his laboratory work, making him comfortable and keeping in the background when he was studying, or by accompanying him to the plague-stricken West Indies, where she was to meet her own death. It is one of life's ironies that her desire to visit France was never realized. Another is that her husband, within a year or two after her death, married a woman as different from her as one human can be from another.