Background: Invasive fungal infection (IFI) is associated with high mortality in lung transplant (LTx) recipients. Data for voriconazole use in preemptive treatment remain scant. Method: A single-center, retrospective cohort study was conducted to investigate the efficacy and safety of voriconazole preemptive treatment for post-LTx colonization. Results: We reviewed 62 adult LTx patients, who received their first course of voriconazole prophylaxis (i.e., as preemptive treatment) between July 2003 and June 2010. Outcomes were determined at 6 and 12 months after commencing therapy. Aspergillus fumigatus (75.8 ) was the most common colonizing isolate. Median duration of voriconazole prophylaxis was 85 days. At 6 months, 1 LTx patient (1.6 ) had IFI, 47 (75.8 ) cleared their colonizing isolate, 3 (4.8 ) had persistent colonization, 7 (11.3 ) had recurrent colonization, 1 (1.6 ) had new colonization, 2 (3.2 ) had aspergilloma, and 1 (1.6 ) was clinically unstable with no culture results. Sixteen (25.8 ) had died by 12 months. Ten (16.1 ) had likely drug-related hepatotoxicity. LTx patients with diabetes mellitus within 30 days before commencing prophylaxis were at higher risk of recurrent Aspergillus colonization at 6 months (P = 0.030). Chronic rejection within 30 days before prophylaxis was associated with 12-month mortality (P = 0.007). Conclusions: Voriconazole preemptive treatment resulted in low incidence of IFI and IFI-related mortality.