Background Trustworthy (i.e. low risk of bias) randomized clinical trials (RCTs) play an important role in evidence-based decision making. We aimed to systematically assess the risk of bias of trials published in high-impact endocrinology journals. Methods We searched the MEDLINE/PubMed database between 2014 and 2016 for phase 2–4 RCTs evaluating endocrine-related therapies. Reviewers working independently and in duplicate used the Cochrane Risk of Bias Tool (CCRBT) to determine the extent to which the methods reported protected the results of each RCT from bias. Results We assessed 292 eligible RCTs, of which 40% (116) were judged to be at low risk, 43% (126) at moderate, and 17% (50) at high risk of bias. Blinding of outcome assessment was the least common domain reported 43% (125), while selective reporting of outcomes was the most common 97% (282). In multivariable analysis, RCTs with a parallel design (OR 2.4; 95% CI; 1.2–4.6) and funded by for-profit sources (OR 2.2; 95% CI; 1.3–3.6) were more likely to be at low risk of bias. Conclusions Trustworthy evidence should ultimately shape care to improve the likelihood of desirable patient outcomes. Six out-of 10 RCTs published in top endocrine journals are at moderate/ high-risk of bias. Improving this should be a priority in endocrine research.