OBJECTIVES:  Glaucoma, a chronic disorder that requires lifelong treatment, creates a financial burden on patient and health care payers. This study compared fixed-combination therapies in patients with open-angle glaucoma, namely, Latanoprost with Timolol (LT), Dorzolamide with Timolol (DT), and Brimonidine with Timolol (BT). METHODS: A cost effectiveness analysis was conducted by extracting data from published literature and primary data collected from pharmacy stores. The study was conducted from a managed care perspective with drug utilization for a period of 12 months. A decision analytic model was developed and incremental cost-effectiveness ratios (ICER) were calculated. Therapy cost was calculated by considering medication cost (by taking an average reimbursement amount provided by Medicare part D and private insurances), physician visit cost, cost associated with adverse drug events, and cost due to lack of patient persistency (based on expected annual drug usage). Effectiveness measure considered was percent reduction in intraocular pressure (IOP) from baseline. A one-way sensitivity analysis was performed by varying cost by 25% to take into consideration the potential wastage, overutilization, underutilization, and various differences in IOP reduction in patients. RESULTS: Mean average percent IOP reduction for LT, DT and BT was 6.3%, 4.3% and 4.6%, respectively. The total cost of therapy for LT, DT and BT was estimated to be $711, $935, and $1099, respectively. ICER analyses indicated a gain of $111.5 for change from DT to LT, while a change from BT to LT indicated a gain of $228. The results remained robust after sensitivity analysis. CONCLUSIONS: In our study, LT was found to be more cost-effective compared to DT and BT. Managed care payers may wish to prioritize fixed-combination therapies used for glaucoma considering medication related adverse events and persistency. Further, research taking into account various other costs should be conducted to provide better evidence.