Consensus as to best practices for the selection, reporting, and interpretation of primary and secondary outcomes of randomized controlled trials is lacking. We reviewed the strategies adopted in publications of randomized controlled trials (RCTs) for the analysis, presentation, and interpretation of efficacy outcomes from a survey of all cardiovascular RCTs published in the New England Journal of Medicine, Lancet, and the Journal of the American Medical Association during 2019. We focus on the choice of primary outcomes, the variety of approaches to selecting secondary outcomes, the options sometimes used to control type I error, and the common practice to not correct for multiple testing in reporting secondary outcomes. We comment on current practice across journals in the reporting of P values and also how conclusions in trial reports frequently adhere to an undue reliance on P < 0.05 as a basis for positive claims of treatment efficacy. We conclude with recommendations for how future RCT reports could best select, report, and interpret their findings on primary and secondary outcomes.