Purpose This study evaluated the incidence of nephrotoxicity due to once daily aminoglycoside (ODA) use in elderly patients at two South Florida institutions. Methods A retrospective review of all patients who received 7 mg/kg/day of either gentamicin or tobramycin was conducted. Results Eighty-one (49%) males and 84 (51%) females with a mean age of 73 (range, 60 to 95) years were included. Nephrotoxicity was evident in 16 patients (9.7%). Of these, eight (4.8%) experienced nephrotoxicity possibly associated with aminoglycoside administration. A subgroup analysis of nonnephrotoxic patients compared with nephrotoxic patients revealed no significant differences in mean initial serum creatinine (1 mg/dL vs 0.95 mg/dL, P = 0.861) or dosing interval (31.4 vs 31.5 hours, P = 0.983). The mean duration of aminoglycoside treatment was less in the nonnephrotoxic group compared with the nephrotoxic group (5.2 vs 9.9 days, P < 0.05). Conclusion The results of this retrospective evaluation suggest that ODA dosing in the elderly is safe; however, patients should be monitored closely, especially when they require more than 5 days of aminoglycoside therapy, or are receiving concomitant nephrotoxic agents.