Ustekinumab was approved for use in the treatment of moderate/severe ulcerative colitis (UC) in 2019. Though it has proven effective in clinical trials, evidence of its effectiveness in clinical practice is limited to the published reports of use in clinical practice. This study assessed ustekinumab effectiveness in patients with UC presenting in real-world clinical practice. Data were drawn from the Adelphi Real World Inflammatory Bowel Disease (IBD) Disease Specific Programme, a cross-sectional survey of physicians and their IBD patients in the USA from December 2022 to January 2024. Physicians provided demographics and clinical characteristics, treatment patterns, symptoms, and remission status for UC patients aged ≥18 years old who were prescribed ustekinumab for >1 day. Analyses were descriptive; McNemar's test was used to compare symptoms and disease severity before and after ustekinumab prescription. Overall, 56 physicians reported on 185 patients. Mean (standard deviation) patient age was 39.7 (12.9) years and 53.0% were female. Most patients were advanced therapy-naïve at ustekinumab initiation (65.9%) and had taken ustekinumab for ≥3 months (84.6%). At survey, 53.0% were in remission defined by Mayo score, and 61.9% were in physician-stated clinical remission. Reports of abdominal pain, bowel urgency, nighttime urgency, and bloody diarrhea were more than halved at survey compared to pre-ustekinumab, with reductions in fatigue and non-bloody diarrhea also seen (all p < 0.0001). Overall, ustekinumab is an effective treatment for UC in real-world clinical practice capable of inducing and maintaining long-term remission. Future work should assess how ustekinumab impacts quality of life.