The recommendation to limit dietary saturated fat intake is primarily drawn from observational studies rather than randomized controlled trials of cardiovascular disease prevention. Thus, we investigated the efficacy of saturated fat reduction in preventing mortality and cardiovascular diseases. In this systematic review and meta-analysis of randomized controlled trials, Cochrane CENTRAL, PubMed, and Ichu-shi databases were searched up to April 2023. Randomized controlled trials on saturated fat reduction to prevent cardiovascular diseases were selected. Cardiovascular and all-cause mortality and cardiovascular outcomes were evaluated. Changes in electrocardiography or coronary angiography findings were excluded because they could be evaluated arbitrarily. Two or more reviewers independently extracted and assessed the data. A random-effects meta-analysis was performed using the Grading of Recommendations Assessment, Development, and Evaluation method. Nine eligible trials with 13,532 participants were identified (two were primary and seven were secondary prevention studies). No significant differences in cardiovascular mortality (RR = 0.94, 95% CI: 0.75–1.19), all-cause mortality (RR = 1.01, 95% CI: 0.89–1.14), myocardial infarction (RR = 0.85, 95% CI: 0.71–1.02), and coronary events (RR = 0.85, 95% CI: 0.65–1.11) were observed between the intervention and control groups. However, due to limited reported cases, we were unable to evaluate the impact of stroke. At present, a reduction in saturated fats cannot be recommended to prevent cardiovascular diseases and mortality. Clinical trials are needed to evaluate the effects of saturated fat reduction under statin administration.