Objectives To evaluate the safety, toleration, and pharmacokinetics (PKs) comparison of two intravenous voriconazole formulations after three ascending dose administrations in healthy Chinese subjects. Methods A randomized, double-blind, placebo- and positive-controlled trial was conducted in three cohorts with a total of 42 healthy Chinese subjects. Every cohort of 14 subjects was allocated in proportion (8:4:2) to test formulation, positive voriconazole or placebo successively by single first and then multiple dose administration of 3 mg/kg, 4 mg/kg, and 6 mg/kg. Key findings A total of 41 subjects completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability with a coefficient of variance of Cmax up to 67.95% and AUC0-τ up to 70.16% and nonlinear pharmacokinetics with a regression coefficient of Cmax of 1.31 and AUC0-τ of 1.75 in a single dose. In the steady state, RAuc (mean±SD) of test drug vs positive control drug of 3 mg/kg, 4 mg/kg, and 6 mg/kg dose group was 5.18±1.07 and 5.26±0.99, 5.59±1.15 and 6.27±0.58, and 5.82±0.47 and 5.52±0.76, respectively; and Rcmax (mean±SD) were 2.50±0.44 and 2.68±0.72, 2.63±0.46 and 3.11±0.57, and 2.79±0.28 and 2.55±0.34, respectively. Adverse events with 37 transient visual disturbances were mainly mild. Conclusions The pharmacokinetics with high interindividual variability, nonlinear characteristics and significant dose-dependent accumulation were comparable in the two formulations. The overall safety of the test formulation was tolerable.