Introduction: Serum lipids variability has been described as a risk factor for cardiovascular disease. However, there is no published systematic review in the literature at the moment. The purpose is to evaluate the association between lipid variability and outcomes related to cardiovascular disease. Methods: We made a systematic search in Pubmed, Science Direct, Clinical Key, CINAHL, Lilacs, and Google Scholar using: lipids, variability, death, stroke, myocardial infarction, and cholesterol variability as keywords. Two independent researchers selected and made an extraction of the data. Non-agreement was solved by a third researcher. Non-language limitations were made. Exposure factors were coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) from LDL, HDL, Non-HDL, Total Cholesterol, and Triglycerides. MACE was the outcome of interest. We made a forest plot and heterogeneity analysis using I2. All analyses were made using STATA v. 14.2 Results: Eight papers from the initial 9785 met the inclusion criteria. All papers were cohort studies and a high heterogeneity was identified in the majority of them. The main heterogeneity causes were the difference in the number of participants in the studies, the years following, and the age of the participants included in the studies. In relation to the studies of low heterogeneity (<40%), we found that the high variability of HDL analyzed with CV increases the risk of myocardial infarction (RR=1.39 [95% CI 1.35-1.42, I2 0%]). On the other hand, there were found significative relations between the variability of HDL analyzed with VIM to cardiovascular disease (RR=1.26 [95% CI 1.20-1.33], however, it had a high heterogeneity (I2 68.4%). Conclusions: The comparisons of the studies that analyze lipid variability have a high heterogeneity due to population differences. A relationship was found in the variability of HDL and myocardial infarction.