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The posaconazole extended release tablet formulation was developed to improve bioavailability relative to the oral suspension. Therapeutic drug monitoring has been used to optimise posaconazole dosing to achieve a target trough level ≥0.7 μg ml−1. We retrospectively evaluated 28 patients with haematological malignancies who received posaconazole tablets for antifungal prophylaxis. Posaconazole serum trough levels were obtained 5 days after initiation of therapy. Mean trough level was 1.19 ± 0.63 μg ml−1, and 71% achieved a trough level ≥0.7 μg ml−1. Diarrhoea was associated with lower mean trough levels (0.65 ± 0.08 μg ml−1 vs. 1.31 ± 0.13 μg ml−1), P = 0.002. Mean trough levels were lower in patients ≥90 kg (0.74 ± 0.09 μg ml−1) vs. <90 kg (1.32 ± 0.14 μg ml−1), P = 0.002 and in patients with body mass index (BMI) ≥30 (0.89 ± 0.13 μg ml−1) vs. BMI <30 (1.29 ± 0.14 μg ml−1), P = 0.05. Posaconazole delayed release tablets attain appropriate trough levels in most patients, but patients with a higher weight and those experiencing diarrhoea are more likely to have lower levels.