Abstract Aims The geographic representation of investigators and participants in heart failure (HF) randomized controlled trials (RCTs) may not reflect the global distribution of disease. We assessed the geographic diversity of RCT leaders and explored associations with geographic representation of enrolled participants among impactful HF RCTs. Methods and results We searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with impact factor ≥ 10 between January 2000 and June 2020. We used the Jonckheere–Terpstra test to assess temporal trends and multivariable logistic regression models to explore associations between predictors and outcomes. There were 414 eligible RCTs. Only 80 of 828 trial leaders [9.7%; 95% confidence interval (CI): 7.8–11.8%] and 453 of 4656 collaborators (9.7%; 95% CI: 8.8–10.6%) were from outside Europe and North America, with no change in temporal trends and with greater disparities in large RCTs. The adjusted odds of trial leadership outside Europe and North America were lower with industry funding [adjusted odds ratio (aOR): 0.33; 95% CI: 0.15–0.75; P = 0.008]. Among 157 416 participants for whom geography was reported, only 14.5% (95% CI: 14.3–14.7%) were enrolled outside Europe and North America, but odds of enrolment were 10-fold greater with trial leadership outside Europe and North America (aOR: 10.0; 95% CI: 5.6–19.0; P < 0.001). Conclusion Regions disproportionately burdened with HF are under-represented in HF trial leadership, collaboration, and enrolment. RCT leadership outside Europe and North America is independently associated with participant enrolment in under-represented regions. Increasing research capacity outside Europe and North America could enhance trial diversity and generalizability.