Amikacin was introduced as the primary aminoglycoside in our hospital to prevent the further development of multiply resistant Gram-negative organisms. This study compares clinical and microbiological data before and after institution of this policy to evaluate the influence on clinical outcome in patients as well as changing resistance patterns in the respiratory ICU. Patient populations were similar in terms of severity of illness (Acute Physiology and Chronic Health Evaluation II scores), age, ventilation, invasive procedures, and the incidence of various diseases. We found that the rate of amikacin resistance increased from 8.5% to 39.6% with an increase in resistance to tobramycin (19.3% to 33.3%) and netilmicin (23.9% to 47.9%) over the same period despite minimal usage of these drugs. The clinical outcome was similar in the periods contrasted. Our findings suggest that restricting aminoglycosides to amikacin only resulted in increasing Gram-negative resistance although there was no significant effect on patient outcome.