Abstract Background Patient participation in clinical trials is vital for knowledge advancement and outcomes improvement. Few adult cancer patients participate in trials. Although patient decision-making about trial participation has been frequently examined, the participation rate for patients actually offered a trial is unknown. Methods A systematic review and meta-analysis using 3 major search engines was undertaken. We identified studies from January 1, 2000, to January 1, 2020, that examined clinical trial participation in the United States. Studies must have specified the numbers of patients offered a trial and the number enrolled. A random effects model of proportions was used. All statistical tests were 2-sided. Results We identified 35 studies (30 about treatment trials and 5 about cancer control trials) among which 9759 patients were offered trial participation. Overall, 55.0% (95% confidence interval CI = 49.4% to 60.5%) of patients agreed to enroll. Participation rates did not differ between treatment (55.0%, 95% CI = 48.9% to 60.9%) and cancer control trials (55.3%, 95% CI = 38.9% to 71.1%; P = .98). Black patients participated at similar rates (58.4%, 95% CI = 46.8% to 69.7%) compared with White patients (55.1%, 95% CI = 44.3% to 65.6%; P = .88). The main reasons for nonparticipation were treatment choice or lack of interest. Conclusions More than half of all cancer patients offered a clinical trial do participate. These findings upend several conventional beliefs about cancer clinical trial participation, including that Black patients are less likely to agree to participate and that patient decision-making is the primary barrier to participation. Policies and interventions to improve clinical trial participation should focus more on modifiable systemic structural and clinical barriers, such as improving access to available trials and broadening eligibility criteria.