The objective of this study was to compare the risk factors and outcome of patients with preexisting resistant gram-negative bacilli (GNB) with those who develop sensitive GNB in the cardiac intensive care unit (ICU). Of the 3161 patients ( n=3,161) admitted to the ICU during the study period, 130 (4.11%) developed health care-associated infections (HAIs) with GNB and were included in the cohort study. Pseudomonas aeruginosa (37.8%) was the most common organism isolated followed by Klebsiella species (24.2%), E. coli (22.0%), Enterobacter species (6.1%), Stenotrophomonas maltophilia (5.7%), Acinetobacter species (1.3%), Serratia marcescens (0.8%), Weeksella virosa (0.4%) and Burkholderia cepacia (0.4%). Univariate analysis revealed that the following variables were significantly associated with the antibiotic-resistant GNB: females (P=0.018), re-exploration (P=0.004), valve surgery (P=0.003), duration of central venous catheter (P<0.001), duration of mechanical ventilation (P<0.001), duration of intra-aortic balloon counter-pulsation (P=0.018), duration of urinary catheter (P<0.001), total number of antibiotic exposures prior to the development of resistance (P=0.014), acute physiology and age chronic health evaluation score (APACHE II), receipt of anti-pseudomonal penicillins (piperacillin-tazobactam) (P=0.002) and carbapenems (P<0.001). On multivariate analysis, valve surgery (adjusted OR=2.033; 95% CI=1.052-3.928; P=0.035), duration of mechanical ventilation (adjusted OR=1.265; 95% CI=1.055-1.517; P=0.011) and total number of antibiotic exposure prior to the development of resistance (adjusted OR=1.381; 95% CI=1.030-1.853; P=0.031) were identified as independent risk factors for HAIs in resistant GNB. The mortality rate in patients with resistant GNB was significantly higher than those with sensitive GNB (13.9% vs. 1.8%; P=0.03). HAI with resistant GNB, in ICU following cardiac surgery, are independently associated with the following variables: valve surgeries, duration of mechanical ventilation and prior exposure to antibiotics. The mortality rate is significantly higher among patients with resistant GNB.