Hypokalemia and hyponatremia are common but easily ignored adverse events in treatment with voriconazole (VCZ) that can lead to serious consequences. We intend to investigate the incidence of VCZ-induced hypokalemia and hyponatremia and their risk factors based on real-world data. A prospective study was conducted. A total of 272 patients with 414 VCZ plasma trough concentrations (C₀) and VCZ N-oxide concentrations (C_N) were included. The incidence of hypokalemia was 18.0% (48/266). A total of 81.2% (39/48) of patients developed hypokalemia within 14 days, whereas 56.2% (27/48) of patients developed hypokalemia within 1 week. The proportion of female patients in the hypokalemia group was higher than that in the nonhypokalemia group, as was the proportion of patients receiving intravenous VCZ. In the multivariate analysis, the independent risk factors for hypokalemia were sex, combined use of antibiotics, and VCZ C_N/C₀. The incidence of hyponatremia was 7.9% (21/266). The proportion of patients over 47 years of age in the hyponatremia group was 71.4% (15/21). The number of days of VCZ use in the hyponatremia group was greater than that in the nonhyponatremia group. A total of 47.6% (10/21) of patients in the hyponatremia group had supratherapeutic VCZ C₀ (>5.0 µg/mL). In conclusion, hypokalemia is more likely to occur in females, in patients receiving intravenous VCZ, and in patients with the combined use of antibiotics. Hyponatremia is more likely to occur in patients older than 47 years who have been using VCZ for a long time and have higher VCZ C₀ values.