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Objective: Amphotericin B is an antifungal agent used to treat serious fungal infections mainly in critically ill patients. Despite its adverse effects including renal toxicity and electrolyte imbalances, amphotericin B remains one of the best choices for antifungal treatment. Information from animal studies has provided a strong scientific basis for the use of pentoxifylline as lowering nephroprotective agent. The present study was designed to evaluate the efficacy of pentoxifylline in preventing renal toxicity and electrolytes imbalances induced by amphotericin B. Methods: This study was conducted as a randomized controlled trial on 44 patients admitted to Sayyedoshohada Hospital, Isfahan, Iran, from October 2016 to August 2018. Patients were assigned to one of the two groups: Pentoxifylline, 400 mg twice a day, or matching placebo, from the 1st day of amphotericin B therapy till minimum of 7 days. All patients' information including lab data (serum and urine levels of Mg, Na, and K, serum creatinine level, blood urea nitrogen [BUN] and urinary creatinine excretion) were gathered at the time of drug initiation and during the study period. The results were analyzed by SPSS v. 20 software and Repeated measures test was used to assess the differences between groups Findings: This study did not show any significant differences between the two groups in terms of all the assessed variables, including serum and urinary levels of electrolytes, and creatinine, as well as the number of cases presented acute kidney injury during the study period. Conclusion: Despite the positive effects of pentoxifylline in preventing renal complications in previous studies, this study could not show a definitive result in salt wasting or renal damage induced by amphotericin B. So, Designing robust studies with more included samples would be valuable.