Background & Aims: There is no reliable standard of disease activity in ulcerative colitis (UC). We performed a prospective study to systematically compare all non-invasive disease activity indices in patients with UC and to identify cutoff scores that correspond to remission and response. Methods: The study included adults with UC (n = 86; 52% males, mean age 37.6 ± 13.7 years). Items from the following indices were scored: partial Mayo score, Rachmilewitz, Lichtiger, Seo, Pediatric Ulcerative Colitis Activity Index (PUCAI), Partial Powell-Tuck, Endoscopic-Clinical Correlation, Beattie, and Walmsley. Physician and patient global assessments, colonoscopic scores, blood test data, and the full Mayo scores were used to assess construct and discriminative validity. A follow-up evaluation of 61 patients was used to assess test-retest reliability and responsiveness. Results: The Walmsley index and PUCAI were best in assessing disease activity, determined by all 4 clinimetric properties. In assessing validity, the mean correlation coefficients for the 5 included constructs were r = 0.80 and r = 0.79 for the Walmsley and PUCAI, respectively (P < .001 for each). The partial Mayo score accurately determined disease activity in 3 of the 4 clinimetric properties; the Rachmilewitz index accurately assessed patients in 2 of the properties. Cutoff scores that defined combined clinical-endoscopic remission and response were determined using receiver operating characteristic curve analyses for all instruments. Conclusions: The Walmsley index and PUCAI are valid, reliable and responsive noninvasive measures to assess disease activity in adults with UC. Given their robust clinimetric properties, use of these indices might permit less-frequent endoscopic assessment in patients with UC-both in research and in clinical practice.