BACKGROUND: Antimicrobial resistance is an increasing problem. OBJECTIVE: To examine the clinical and economic impact of antibiotic resistance in Pseudomonas aeruginosa. METHODS: In-hospital mortality, secondary bacteremia, length of stay, and hospital charges were examined in a cohort of 489 inpatients with positive clinical cultures for P aeruginosa. One hundred forty-four had a resistant baseline P aeruginosa isolate and 30 had resistance emerge during follow-up. Multivariable and survival analytic methods were used to adjust for confounding and effects of time. RESULTS: The overall in-hospital mortality rate was 7.6%, 7.7% in patients with a resistant isolate at baseline (relative risk [RR], 1.3; 95% confidence interval [CI], 0.6-2.8) and 27% in patients in whom resistance emerged (RR, 3.0; 95% CI, 1.2-7.8). Secondary bacteremia developed in 1.4% of patients in whom resistance did not emerge and in 14% of those in whom resistance emerged (RR, 9.0; 95% CI, 2.7-30). The median duration of hospital stay following the initial P aeruginosa isolate was 7 days. Emergence of resistance, but not baseline resistance, was significantly associated with a longer hospital stay (P<.001 and P=.71, respectively). The average daily hospital charge was $2059. Neither baseline resistance nor emergence of resistance had a significant effect on the daily hospital charge. In a matched cohort analysis, a trend was seen toward increased total charges in patients demonstrating emergence of resistance (difference, $7340; P=.14). CONCLUSIONS: Emergence of antibiotic resistance in P aeruginosa results in severe adverse outcomes. Efforts should be directed toward early detection and prevention of emergence of antibiotic resistance.