Background <p>Endometriosis is a chronic gynecological condition associated with pelvic pain, dysmenorrhea, dyspareunia, and impaired quality of life. Medical management aims to reduce symptoms and prevent recurrence. The primary objective of this study was to compare the efficacy of Dienogest versus Oral Contraceptive Pills (OCPs) in controlling endometriosis-associated pelvic pain. The secondary objective was to compare the improvement in health-related quality of life (QoL) between the two groups.</p> Methods <p>This prospective cohort study included 80 women with histologically confirmed endometriosis, divided in two groups. Group I (<i>n</i> = 40) received Dienogest 2&#xa0;mg daily, and Group II (<i>n</i> = 40) received an OCP containing ethinyl estradiol 0.03&#xa0;mg and drospirenone 3&#xa0;mg daily for 24 weeks. The primary outcome was the change in endometriosis-associated pelvic pain from baseline to the end of treatment assessed using the total symptoms and sign severity score (Biberoglu and Behrman score).</p> Results <p>Baseline demographic and clinical characteristics were similar between groups (<i>p</i> &gt; 0.05). Both treatments significantly improved pelvic pain, dysmenorrhea, and dyspareunia (<i>p</i> &lt; 0.001). However, Dienogest demonstrated greater reduction in total symptoms and sign severity scores (mean difference 5.3 vs. 3.82, <i>p</i> &lt; 0.001) and higher percentage improvement (64.2% vs. 48.1%, <i>p</i> = 0.002). More patients in the Dienogest group shifted to mild/moderate severity (<i>p</i> = 0.04). EHP-30 scores showed significantly better post-treatment improvement with Dienogest (mean reduction 19.4 vs. 12.3, <i>p</i> &lt; 0.001).</p> Conclusion <p>Both Dienogest and OCPs effectively reduce endometriosis-associated pain, but Dienogest provides superior improvement in symptom severity and quality of life, supporting its use as a more effective long-term therapeutic option.</p>