Oral isotretinoin causes changes in serum lipid values. These changes are not seen in every patient, regardless of dose. It is unclear what causes these changes and how often serum lipid values should be followed up. We aimed to evaluate the relationship between the change in serum lipid values and personal and familial risk factors. Serum lipid values at baseline (0th), 1st, 3rd, and 6th months of isotretinoin treatment of acne patients aged 16 years and over using oral isotretinoin at a dose of 0.5-1mg/kg/day between January 2017 and December 2019 were recorded retrospectively. The relationship between personal and familial risk factors and changes in serum lipid values were evaluated statistically. In pairwise comparison, a significant difference was detected between the 0th and 1st month, 0th and 3rd month, 0th and 6th month, and 1st and 6th month in the average serum lipid (Low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), total cholesterol, triglyceride) levels. However, no significant difference was detected between 3rd and 6th month. The change in LDL levels between the 0th and the 3rd month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.034). The change in VLDL levels between the 0th and 6th month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.022). It was observed that the changes in total cholesterol and VLDL levels between the 0th and 3rd month increased as body mass index (BMI) increased (p = 0.03, p = 0.014, respectively). Similarly, the changes in triglyceride and VLDL levels between 0th and 6th month and between 1st and 6th month increased by an increase in BMI (respectively; p = 0.006, p = 0.019; p = 0.016, p = 0.022). The increase in the levels of VLDL between the 1st and the 6th month was found to be significantly higher in smokers than in non-smokers (p = 0,032). We recommend evaluation of serum lipids values in the 0th,1st, and 3rd month in all acne patients using oral isotretinoin and that these values have to be checked monthly in the following months for smokers, those with a history of atherosclerosis, and those with a BMI above normal.