Objectives To determine whether interstitial cystitis/painful bladder syndrome (IC/PBS) in women is associated with antecedent sexual and reproductive characteristics. Methods By multivariate analyses, 312 incident IC/PBS cases were compared with matched controls for antecedent sexual and reproductive characteristics, adjusted by demographics, previous surgery, and nonbladder syndromes (NBSs), such as chronic pelvic pain, irritable bowel syndrome, and panic disorder. Results IC/PBS was significantly associated with previous female hormone use, a history of fewer pregnancies (in premenopausal women), and antecedent NBSs, especially when expressed by the number of such syndromes. Conclusions Three antecedents to IC/PBS were prominent. Female hormone use was consistent with a pharmacologic effect or as a marker of its indications. A history of fewer pregnancies among premenopausal, but not postmenopausal, women with IC/PBS was consistent with pregnancy postponing the occurrence of IC/PBS, a marker for decisions to avoid pregnancy, or a result of recruitment bias. NBSs, especially the total number experienced by the participant, had the strongest correlation with IC/PBS. This finding suggests that knowledge of the pathogeneses of these NBSs, many of which are functional somatic syndromes, might reveal that of IC/PBS. © 2011 Elsevier Inc.