OBJECTIVE To compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis. METHODS A randomized double-blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups. RESULTS Treatment with dienogest or COCP was associated with improved self-reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post-hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004). CONCLUSIONS Postoperative administration of dienogest or COCP reduced endometriosis-associated pain and improved quality of life in women with severe endometriosis. BACKGROUND https://en.irct.ir/trial/43070.