OBJECTIVES: Patients with open-angle glaucoma (OAG) whose intraocular pressure was not adequately controlled by one medication have several alternate treatment options. This analysis evaluated the direct costs in the US of unilateral eye treatment with two trabecular micro-bypass stents (two stents) compared to selective laser trabeculoplasty (SLT) or medications only over 5 years post-initiation. METHODS: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related direct costs over 5 years. Patients were modeled to initiate treatment in year zero with two stents, SLT, or medications only. In years 1 through 5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications. RESULTS: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm ($4,024) compared to the SLT arm ($4,040) or medications only arm ($5,066). Initial year zero costs were higher with two stents ($2,674) than with SLT ($829) or medications only ($806). Average marginal annual costs in years 1 through 5 were $270 for two stents, $642 for SLT, and $852 for medications only. The cumulative costs difference between two stents versus SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two stents over SLT or medications only was $16 or $1,042, respectively. CONCLUSIONS: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Five-year cumulative costs in the two-stent treatment arm were approximately equivalent to the SLT arm, and showed savings compared to the medications only arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons.