Fifty-six serum posaconazole trough levels were measured in 17 cardiothoracic transplant recipients. Initial levels were ≤ 0.5, 0.51 to 0.99, and ≥ 1 μg/ml for 47, 29, and 24% of patients, respectively. Median trough levels associated with therapeutic success were higher than those associated with failure (1.55 versus 0.34 μg/ml; P = 0.006). Patients with levels consistently >0.5 μg/ml were more likely to have successful outcome (P = 0.055). Age ≥ 65 years, oral administration, and absence of proton pump inhibitors were associated with higher levels of posaconazole (P = 0.006, 0.006, and 0.001, respectively).