BACKGROUND: Isavuconazole (ISCZ) is an azole antifungal with a low risk of QTc prolongation and no requirement for renal dose adjustment. However, real-world data in Asian patients remain limited. METHODS: We retrospectively evaluated 45 patients who received ISCZ between April 2023 and March 2025. Laboratory parameters and QTc values (QTcB/QTcF) were extracted from medical records. Longitudinal changes were assessed using linear mixed-effects models. In patients receiving arsenic trioxide (ATO), QTc trajectories were compared among ATO alone, ATO with ISCZ (ATO-ISCZ), and ATO with other antifungals. RESULTS: Grade ≥2 elevations in AST and ALT occurred in 11.1% and 13.3% of patients, respectively, and were transient. No significant deterioration in laboratory parameters was observed. In the ATO subgroup, QTc values in the ATO-ISCZ group were lower than those in the ATO group from Day 30, with the largest difference at Day 70 (-45.5 ms for QTcB and -42.3 ms for QTcF; both p < 0.001). The ATO-other antifungals group showed similar trends to the ATO group. No clinically significant cardiac events were observed. CONCLUSIONS: ISCZ showed a favorable safety profile in Japanese patients with hematologic malignancies and may be a safe option during QT-prolonging therapies.