OBJECTIVES: Persistent attachment between the vitreous and the macula causes vitreomacular traction (VMT) and subsequent formation of a macular hole (MH) leading to symptomatic loss of visual function. This analysis estimated long-term benefits and costs associated with the resolution of traction following treatment with ocriplasmin versus standard-of-care (observation, followed by vitrectomy if needed), in the French healthcare system, from a collective perspective.  METHODS: The model included (1) a short-term decision-tree, simulating 6-month anatomical and visual outcomes observed in the two Phase III MIVI-TRUST ocriplasmin randomized controlled trials (RCTs), and (2) a long-term Markov state-transition model, tracking patients over a lifetime-period. Both models were linked through common health states based on VMT resolution or MH closure, number of vitrectomies and visual acuity status. Effectiveness and safety outcomes were based on the MIVI-TRUST RCTs. Patient populations included (1) total licensed VMT population, independent of the presence/absence of a MH, and two subgroups according to pre-specified analyses (2) VMT with epiretinal membrane (ERM), and (3) VMT without ERM. Benefit was measured in quality-adjusted life years (QALYs), based on (1) time spent in health states defined by the visual acuity of the best and worse seeing eye, (2) disutility impact associated with surgical interventions (vitrectomy and cataract), adverse events and metamorphopsia. Resources used with ocriplasmin and standard-of-care were based on expert opinions. Unit costs were mainly drawn from the French national hospital database.  RESULTS: Over a life-time, ocriplasmin versus standard-of-care generated incremental benefits in terms of QALYs and overall treatment costs in group (1) 0.071; €2,107 (2) 0.034; €2,689, and (3) 0.093; €1,757. Lifetime per-patient cost/QALY was €29,767; €78,393, and €18,917, respectively.  CONCLUSIONS: Applying commonly accepted cost-effectiveness thresholds (€35,000-€50,000/QALY), this first French cost-utility analysis shows that ocriplasmin represents a cost-effective strategy in total licensed VMT population, and particularly in patients without ERM.