Abstract Background Despite recent progress, inflammatory bowel disease (IBD) therapies with pronounced long-term efficacy and improved safety are needed. IBD clinical trials face challenges with patient recruitment because of study designs, competitive or overlapping trials, and limited numbers of eligible patients. We aimed to better understand patients’ awareness of, attitudes toward, and experience with IBD clinical trials. Methods This multinational, cross-sectional cohort study of adults with IBD recruited online consisted of 2 components: a quantitative 15-minute online survey completed by all participants and a qualitative 30-minute telephone interview completed by a subset of patients from the United States. Results Quantitative survey respondents (N = 226) included patients with ulcerative colitis (52%) and Crohn’s disease (48%) from the United States (n = 100, 21 of whom were interviewed), Brazil (n = 26), Canada (n = 25), France (n = 25), Germany (n = 25), and Spain (n = 25); 96% of respondents reported at least a basic understanding of clinical trials. Patients rated conversations with health care providers most helpful for researching trials, but during interviews patients discussed their desire for increased patient–physician communication about trials. Major barriers to participation included invasive screening/monitoring (35% of quantitative responses) and concern over receiving placebo (35%) or suboptimal treatment (33%). Most respondents (68%) reported that clinical trial participants are “guinea pigs” for an experimental treatment. Conclusions Opportunities to improve participation in IBD trials include improved communication with health care providers, further patient education, and alternative trial designs. Ultimately, a better understanding of the patient perspective will be important for more informed patients and more successful recruitment and enrollment.