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Introduction: Medium-term survival and functional outcome of patients requiring prolonged mechanical ventilation (PMV) ≥ 21 days after lung transplantation (LTx) remain unclear. Objectives and Methods: We conducted a post hoc analysis on a cohort of 82 adults patients who underwent consecutively LTx at the University Hospital of Marseille from January 2008 to May 2011 and who survived above 21 days postoperative. The main objectives were 1/to identify risk factors of VMP by univariate and multivariate analysis; 2/ to evaluate the impact of VMP on survival and functional outcome at 3 years after LTx. Results: 34 recipients required a PMV and 48 recipients did not (control group). Median duration follow-up was 1428 ± 847 days. Multivariate analysis identified graft volume reduction as the main independent risk factor for PMV (OR: 14.61, 95%CI: 1.35-157, p=0.02). Significant decrease in survival at 1, 2 and 3 years was observed in PVM group compared to controls (73.5%, 61.2%, 51% vs . 85.4%, 82.5%, 77.9%). Lung function was significantly impaired in PMV recipients compared to controls at 1 yr and 3 yrs with lower values of FEV1 (1681 ± 919ml and 1759 ± 250 ml vs. 2625 ± 1132 ml and 2626 ± 186 ml, p vs. 3450 ± 1176 ml and 3425 ± 188 ml, p vs. 555 ± 114 m and 564 ± 21 m) respectively. However no significant difference in the development of chronic allograft dysfunction at 3 yrs was observed between the 2 groups. Conclusion: Graft volume reduction was the main predictive factor of PMV. PMV limited recipient9 survival and lung functional outcome at medium-term after LTx.