Abstract Aims Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. Methods and results Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of −0.34 mmol/L (95% confidence interval, −0.44, −0.23; P = 1 × 10−9), −0.30 mmol/L (−0.40, −0.19; P = 4 × 10−8), and −12.92 mg/dL (−22.63, −3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels. Conclusion Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B—effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease. Structured Graphical Abstract Structured Graphical Abstract Overall aim, methods, and findings of the study. The flowchart in left, lower corner visualizes the study selection process. The items on the right side visualize the meta-analysed effects of vegetarian and vegan diets on levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B.