e12516 Background: Incorporating adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitors abemaciclib and ribociclib along with endocrine therapy has been shown to improve invasive disease-free survival (iDFS) for hormone receptor-positive (HR+) human epidermal receptor 2 negative (HER2-) early breast cancer (EBC). This study assesses the cost-effectiveness of this strategy, along with adjuvant aromatase inhibitors (AI) from an Indian perspective. Methods: A Markov chain model evaluated the cost-effectiveness of abemaciclib and ribociclib with letrozole compared to letrozole alone for HR+/HER2- EBC from a payer perspective in India. Key measures included lifetime quality-adjusted life years (QALY), life-years (LY), and total costs. This study explores two scenarios for effectiveness: a best-case (BC) scenario, where the benefit of CDK4/6 inhibitors in improving iDFS lasts a lifetime, and a worst-case (WC) scenario, where benefits disappear after 5 years. Probabilistic sensitivity analyses (PSA) were used to account for simulation uncertainty. Results: In the BC scenario, abemaciclib added 2.17 QALY and 4.96 LY, costing $27,756.65 more. Ribociclib in the BC scenario added 0.98 QALY and 2.58 LY, with added costs of $20,494.6. The incremental cost-effectiveness ratio for abemaciclib and ribociclib surpassed the willingness to pay threshold for in India in both scenarios (Table). At current market prices there is 0% probability of cost-effectiveness of abemaciclib and ribociclib. The cost of abemaciclib and ribociclib needs to be reduce by 78.61% and 87.19%, respectively to achieve cost-effectiveness. Conclusions: The combination of adjuvant abemaciclib or ribociclib with letrozole is not cost-effective for HR+/HER2- EBC in India in either the best or worst-case scenario.[Table: see text]