OBJECTIVES: Topical prostaglandin analogs combined with timolol demonstrate strong intra-ocular pressure lowering effect and are indicated in second line treatment.  This study aims to estimate the 5-years cost effectiveness of Duotrav® and Xalacom® in second line glaucoma treatment in France from the perspective of the health care system. METHODS: A 5 year Markov model was built to populate the treatment of two cohorts of glaucoma patients. Time to treatment modification, a key cost factor in real life, was estimated on the basis of an analysis of the UK GPRD database and a hazard-ratio (DuoTrav vs Xalacom) taken from a French observational study. Visual field defect (VFD) occurrence rathes by treatment line were estimated from the literature. French standard costs were applied. Sensitivity analyses were carried out.  RESULTS: Average times to treatment changes were 38.0 and 31.1 months for Duotrav and Xalacom, respectively. A total of 45.4% of the patients remained with their treatment at 5 years in the Duotrav cohort compared with 29.1% in the Xalacom group.  The clinical benefit of Duotrav was 0.06 less new VFDs on average per patient. The longer duration of treatment with Duotrav was associated with an extra costs of €144, an amount that was totally offset by a decrease in operating procedures (-€98.7) and cost of rescue medications (- €98.5). Other resources used (visits, exams..) were similar. Total costs were lower in the Duotrav cohort (-€81.8) than in the Xalacom cohort. Sensitivity analyses confirmed these findings. CONCLUSIONS: Treatment persistency is a key indicator of the effectiveness of chronic disease treatment in daily practice. The longer duration of treatment with Duotrav as compared with Xalacom lead to better glaucoma control, less VFD progression, and lower medical care costs. According to this analysis, DuoTrav economically dominates Xalacom.