Abstract Background Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Methods Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients’ having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Results Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72–2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25–1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26–1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. Conclusions For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.