Objective: Oral contraceptives are the second-most widely used contraceptives in Indonesia; however, a high percentage rate of withdrawal is seen owing to adverse drug reactions (ADRs). Only a small proportion of users have been provided information about other oral contraceptives such as newer generation progestin as an alternative option to minimize ADR. This study aimed to compare the prevalence of ADR between combined oral contraceptives containing levonorgestrel (LNG) (second generation) and desogestrel (DSG) (third generation), which was expected to have less side effects. Methods:The study has a cross-sectional comparative design with random sampling from users in six villages in Depok City, Indonesia. Data were collected through interviews. The sample includes 60 users of LNG and 40 users of DSG.Results: ADR complaints include intermenstrual bleeding (16.7% vs. 5%), headache (16.7% vs. 5%), nausea/vomiting (25% vs. 0%), breast tenderness (13.3% vs. 0%), impaired sexual intercourse (23.3% vs. 7.5%), weight gain (35% vs. 22.5%), acne (3.3% vs. 7.5%), and face spots/chloasma (28.3% vs. 5%). The LNG group showed significantly higher impaired sexual intercourse (odds ratio (OR): 3.75, 95% confidence interval (CI): 1.003-14.050, p=0.039) and chloasma (OR 7.51, 95% CI: 1.629-34.647, p=0.004). Conclusion:Users' low knowledge of ADR and how to treat it could be a reason for drug withdrawal. Pharmacies must make efforts to provide counseling in this regard.