BACKGROUND Pain perception is critical for detection of noxious bodily insults. Gastrointestinal hypoalgesia in inflammatory bowel disease (IBD) is a poorly understood phenomenon previously linked to poor patient outcomes. We aimed to evaluate the risk factors associated with this condition and to discern characteristics that might differentiate these patients from pain-free quiescent counterparts. METHODS We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 3 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: a) active IBD without pain (hypoalgesic IBD); b) active IBD with pain; and c) inactive IBD without pain. RESULTS One hundred fifty-three IBD patients had active disease and 43 (28.1%) exhibited hypoalgesia. Hypoalgesic IBD patients were more likely to develop non-perianal fistulae (P=0.03). On logistic regression analysis, hypoalgesic IBD was independently associated with male sex, advancing age and mesalamine use, and inversely associated with anxious/depressed state and opiate use. Hypoalgesic IBD patients were demographically and clinically similar to the pain-free quiescent IBD cohort (n=59). Platelet count and C-reactive protein were more likely to be pathologically elevated in hypoalgesic IBD (P=0.03), though >25% did not exhibit elevated inflammatory markers. CONCLUSIONS Hypoalgesia is common in IBD, particularly in male and older individuals, and is associated with an increased incidence of fistulae and corticosteroid use. Novel noninvasive diagnostic tools are needed to screen for this population, as inflammatory markers are not always elevated.