BACKGROUND: The current study was aimed at updating prior systematic review and meta-analyses (SRMA) in order to determine the effects of supervised exercise-based cardiac rehabilitation (EBCR) and introduce a suitable exercise protocol for lipid profile changes in patients with cardiovascular disease (CVD).METHODS: PubMed, Scopus, and Web of Science databases were searched from 1980 to December 2018. All published, randomized controlled trials (RCTs) reporting the efficacy of supervised EBCR in patients with CVD and measuring at least 1 component of lipid profile were included. The quality of articles was assessed based on the Physiotherapy Evidence Database (PEDro) scale. Random effect model was used to calculate the effect size of post-intervention data.RESULTS: Initially 774 RCTs were reviewed, 14 of them were included in the study. In comparison with the control group, supervised EBCR was associated with higher serum levels of high-density lipoprotein (HDL) [weight mean difference (WMD): 1.297; 95% confidence interval (CI): -1.620, 4.214] and lower serum level of low-density lipoprotein (LDL) (WMD: -7.797; 95%CI: -14.005, -1.588), total cholesterol (TC) (WMD: -11.029; 95%CI: -20.716, -1.342), and triglyceride (TG) (WMD: -14.602; 95%CI: -28.992, -0.212).CONCLUSION: It seems that EBCR is correlated with an insignificant increase in HDL serum level and a significant decrease in LDL, TC, and TG serum levels. Considering subgroup analysis results, it is suggested that long duration, moderate exercise volume (EV), and combination of aerobic exercise (AE) and resistance exercise (RE) be used to improve HDL and TG serum levels. Short duration, high EV, and AE+RE seem to significantly reduce LDL serum level. Moreover, moderate EV is associated with a significant reduction in TC level.