BACKGROUND: We aimed to evaluate the effectiveness and safety of risankizumab (RZB) for Crohn's disease (CD) in routine clinical practice. METHODS: We performed a retrospective review of a multicenter consortium of CD patients treated with RZB. Co-primary outcomes were week 12 clinical remission (Harvey Bradshaw Index [HBI] score of </=4 or physician global assessment in those without HBI or with ileostomy) and 6-month endoscopic remission (Simplified Endoscopic Mucosal Assessment for Crohn's Disease of 0-1 or absence of ulcers). Secondary outcomes included steroid-free clinical remission, clinical response, radiographic response, cumulative clinical and endoscopic remission rates at 6 and 12 months, and adverse events. RESULTS: A total of 309 patients were included (median disease duration 14 years [IQR, 6-24]; median follow-up 7.1 months [IQR, 4.1-10.3]). Most patients (85.8%) were advanced therapy (AT)-exposed, and 169 (54.7%) had prior ustekinumab (UST) exposure. Week 12 clinical remission rates were 49.7% (98/197) overall, and 44.2% (50/113) vs 57.1% (48/84) in UST-exposed vs naive patients (P = .073). Among those with active disease on baseline endoscopy (n = 122) who had an available follow-up at 6 months, 52.4% (22/42) achieved endoscopic remission. Cumulative rates of clinical and endoscopic remission at 12 months were 65.0% and 49.5%, respectively. Cumulative 12-month endoscopic remission was 33.9% (19/56) in UST-exposed and 68.1% (32/47) in UST-naive patients (P < .001). Risankizumab was well-tolerated with no new safety signals identified. CONCLUSIONS: In this large multicenter cohort of patients with CD, RZB was well-tolerated and effective in achieving favorable clinical and endoscopic outcomes in both AT-exposed and naive populations, including those with exposure to UST.