Background: We assessed the effects of cisplatin-based chemotherapy, magnesium supplementation, probable contributory factors such as cisplatin cumulative dose and dose per cycle on serum magnesium levels.Methods: In this prospective randomized study, serum magnesium levels of 59 newly diagnosed adult patients receiving cisplatin-based chemotherapy were studied. The patients were randomly allocated to receive magnesium supplementation at a dose of 5 g IV per cycle (n=31) or to a control group (n=28). Serum magnesium levels <1.8 mg/dL were considered to indicate hypomagnesemia.Results: The decrease in mean magnesium levels with continuing chemotherapy courses was significant in both groups with a more prominent decrease in the control group. In courses 4 and 5, mean magnesium levels were significantly higher among those who received magnesium supplementation than in the control group. Thirty patients (50.8%) had at least one incident of hypomagnesemia after beginning chemotherapy. All hypomagnesemia incidents were mild (mean 1.69, range; 1.52-1.79 mg/dL). Hypomagnesemia was more frequent in the control group (38.7% vs. 60.7%, P=0.09). Although age and sex had no significant effect on the incidence of hypomagnesemia, more hypomagnesemia incidents were observed in patients who received cisplatin in a single loading dose than in those who received the drug in divided doses for each cycle (71.4% % vs. 42.9%, P=0.056).Conclusion: Magnesium supplementation at a dose of 5 g per cycle partially compensated for cisplatin- induced magnesium loss. Monitoring magnesium levels and magnesium supplementation is warranted, especially for those undergoing protracted courses of cisplatin-based chemotherapy. Patients who receive the drug in a single loading dose might be more prone to magnesium loss.