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Voriconazole (VRC) overdoses are frequent and expose patients at high risk of adverse effects. This case–control study performed in hematological patients who benefited from VRC therapeutic drug monitoring from January 2012 to December 2015 aimed to identify risk factors of VRC overdose. Pharmacogenetic, biological, and demographic parameters at the time of VRC trough concentration (C_min) were retrospectively collected from medical records. Cases (VRC overdose: defined by a VRC C_min ≥ 4 mg/L; n = 31) were compared to controls (no VRC overdose: defined by VRC C_min < 4 mg/L; n = 31) using nonparametric or chi‐square tests followed by multivariable analysis. VRC overdoses were significantly associated with high CRP and bilirubin levels, intravenous administration, and age in univariable analysis. In contrast, the proportion of CYP genotypes (CYP2C19, CYP3A4, or CYP3A5, considered …