Objective To test the hypothesis that more bladder pain syndrome/interstitial cystitis (BPS/IC) cases than controls report pre-onset urinary symptoms. Methods In a risk factor study, the date of BPS/IC onset (index date) was systematically determined in 312 female incident cases; the mean age at onset was 42.3 years. Frequency-matched controls were compared on pre-index date medical history. Results Three pre-index date symptoms were more common in BPS/IC cases: pelvic pain with urinary features, frequency, and bladder pain; 178 cases (57%) vs 56 controls (18%) had at least 1 symptom (P <.001). Several perspectives suggested that prodromal symptoms were different from BPS/IC symptoms. In prodromal women, the median age of the earliest urinary symptom "more than other people" was 20 years. Women with the prodrome were significantly more likely than those without to have pre-index date nonbladder syndromes (NBSs). The prodrome predicted not only BPS/IC but also a worse prognosis for it. Conclusion Before the onset of BPS/IC, pelvic pain with urinary features, frequency, and/or bladder pain were reported by more than half the cases. Prodromal women recalled abnormal urinary symptoms decades before the onset of BPS/IC. The prodrome was associated with prior NBSs and predicted not only BPS/IC but also its poor prognosis. These data generated 2 hypotheses: that (1) prodromal symptoms are different from BPS/IC symptoms and (2) pain amplification links NBSs, the prodrome, the appearance of BPS/IC, and its poor prognosis. Recognition of the prodrome might provide opportunities for prevention of fully developed BPS/IC. © 2014 Elsevier Inc All Rights Reserved.