Patients prescribed liposomal-amphotericin B (L-AMB) frequently require supplemental potassium to prevent hypokalemia. The aim of this retrospective study was to examine the appropriate potassium supplementation conditions to treat hypokalemia induced by L-AMB. The subjects were 100 hematological patients who received L-AMB for the first time between April 2012 and March 2013. A total of seven patients were excluded. Of the remaining 93 patients, 48 (51.6%) were assigned to the group receiving supplemental potassium (supplementation group), and 45 (48.4%) were assigned to the group without potassium supplementation (non-supplementation group). Hypokalemia greater than grade 3 was exhibited by 50 of the 93 (53.8%) patients. Multivariate analysis revealed that the minimum serum potassium levels during L-AMB administration (≤2.98 mEq/l) were an independent factor significantly contributing to the effectiveness of potassium supplementation [odds ratio (OR), 3.62; 95% confidence interval (CI), 1.44–9.59; P<0.01]. In addition, multivariate analysis revealed that the serum potassium levels (≥2.83 mEq/l) prior to the potassium supplementation were an independent factor significantly contributing to the development of proper potassium supplementation (OR, 14.21; 95% CI, 1.95–310.72; P=0.02), and no significant difference was observed in the dosage of the potassium supplementation administered to the patients who recovered from hypokalemia and those who did not. In conclusion, it is necessary to begin potassium supplementation prior to the reduction of the serum potassium levels to <2.83 mEq/l. Potassium supplementation at an early stage of L-AMB treatment is important to prevent severe electrolyte abnormalities.