OBJECTIVES:  Ulcerative colitis (UC), an inflammatory bowel disease, substantially impacts patients’ health-related quality of life (HRQL). The SF-36® Health Survey (SF-36), a generic health status measure, quantifies the impact of UC on HRQL, though to-date there is no summary of evidence of its psychometric properties for this purpose. A systematic review of the literature evaluated the SF-36 as a valid and responsive measure of HRQL in UC. METHODS:  We searched PubMed, EMBASE, Cochrane CENTRAL, and BIOSIS Weekly databases. Search terms included ‘ulcerative colitis’, ‘inflammatory bowel disease’, SF-36, and HRQL. English-language articles reporting SF-36 findings from UC-only samples were selected. When possible, SF-36 mean scale scores were extracted and converted to norm-based T-scores and summarized across studies. RESULTS: Fifty-nine articles meeting all criteria were reviewed. Evidence supported the following: (1) adequate internal consistency (Cronbach’s α≥0.70) and test-retest reliability (intraclass correlations ≥0.70) for most SF-36 scales; (2) moderate-to-strong correlations between SF-36 scales and disease-specific HRQL instruments (mean r: 0.45 to 0.65) and the Colitis Activity Index, a disease activity measure (mean r: -0.26 to -0.60, with absolute values >0.50 for Bodily pain, Vitality, and Social functioning scales); (3) clinically meaningful differences across UC patients grouped by disease activity status and symptoms (i.e., differences that exceed the established group-level minimal clinically important difference thresholds [ranging 2 – 4 points across scales]); and (4) responsiveness to treatment, indicated by statistically significant treatment-arm differences for most SF-36 scales in randomized-controlled trials. CONCLUSIONS:  The SF-36 has strong psychometric properties when used with UC patients. Across studies, SF-36 scales showed robust associations with clinical measures of disease activity. The SF-36 also reflected improvements following treatments that reduced UC activity and severity. Results support the inclusion of the SF-36 as an endpoint in randomized-controlled trials for UC patients to evaluate the effect of treatment on patients’ generic health status.