Aim: Impact of gender on aminoglycoside induced nephrotoxicity is still controversial and inconclusive. The objective of this study was to investigate the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in male and female hospitalized patients. Methodology: A one-year, non-interventional prospective study of patients administered either GM or AK. The study was carried out at the internal medicine department of Al-Watani governmental hospital. Nephrotoxicity was defined as a blood creatinine (Cr) increase of 0.5 mg/ dL from the basal (normal) Cr level. Data were entered and analyzed using SPSS 16. Results: A total of 94 patients were identified (GM, n = 45 and AK, n = 49). Male and female patients on GM had comparable characteristics except that males had significantly higher number of co-existing chronic diseases. No gender differences were observed in gentamicin induced nephrotoxicity (37% in males versus 33.3% in females, P = 0.8). Male and female patients on AK were also comparable in demographic and clinical characteristics. However, significant differences in gender susceptibility were observed with AK induced nephrotoxicity (31.6% in females versus 6.7% in males, P = 0.043). Pattern of serum creatinine changes in patients on GM were comparable between males and females. However, in females on AK, s.cr levels were rising sharply after the fourth day compared with that in male patients on AK. Conclusion: Gender differences in aminoglycoside induced nephrotoxicty were seen with AK where females were more vulnerable to nephrotoxicity. Such gender differences did not exist with GM.