OBJECTIVES: To compare the costs and effectiveness of two treatment sequences, Xalatan®-Xalacom® (X-X) versus Travatan®-DuoTrav® (T-D), in the treatment of glaucoma or ocular hypertension (OHT). METHODS: A discrete event simulation (DES) model was constructed. Patients with either glaucoma or OHT were treated first-line with a prostaglandin, either Xalatan® or Travatan®. In case of treatment failure, patients were switched to the specific prostaglandin-timolol sequence Xalacom® or DuoTrav®. Failure was defined as intraocular pressure higher than 18 mmHg (Advanced Glaucoma Intervention Study) at 2 visits. ‘Time to failure' was estimated from two randomized clinical trials (Xalatan® versus Travatan®, Xalacom® versus DuoTrav®). Log-rank tests were computed. Exponential functions were used to model ‘time to failure'. The economic perspective was that of society in France. The time horizon of the model was 60 months. Resource utilizations were estimated from a national French observational survey. Outcomes included treatment failure and disease progression. Sensitivity analyses were performed. RESULTS: Xalatan® treatment resulted in more treatment failures than Travatan® (p<0.007), and Xalacom® more than DuoTrav® (p<0.04). At 60 months, the probability of starting a third treatment line was 39.0% with X-X versus 25.1% with T-D. On average, X-X patients developed 0.51 new visual field defects versus 0.43 for T D patients. The probability of no disease progression at 60 months was 64.2% with X-X and 69.2% with T-D. The 5-years costs of X-X and T-D patients were 3,220 euros and 3,184 euros, respectively (Travatan® price was 114% Xalatan®; Xalacom® and DuoTrav® prices were hypothesized as equal).CONCLUSIONS: Based on well-controlled randomized clinical trial results and using a DES model, the T-D sequence was economically dominant over the X-X sequence.