BACKGROUND Whether the combination of antimicrobial therapy is a factor in mortality in Pseudomonas aeruginosa bacteremia remains to be elucidated. This study investigated the risk factors for mortality in P. aeruginosa bacteremia patients and the influence of adequate antimicrobial therapy and combination therapy on clinical outcomes. METHODS This retrospective study analyzed data of 234 patients with P. aeruginosa bacteremia at a 1,200-bed tertiary teaching university hospital in South Korea between January 2010 and December 2012. Factors associated with mortality were determined. Mortality was compared in patients with adequate empirical and targeted combination therapy, and monotherapy, and inappropriate therapy. RESULTS A total of 141 (60.3%) patients were given appropriate empirical antibiotic treatment (combination therapy in 38 and monotherapy in 103). Among 183 patients (78.2%) who finally received appropriate targeted treatment, 42 had combination therapy and 141 had monotherapy. The percentage of patients receiving empirical combination therapy was slightly, but not significantly higher, in the survivor group than in the nonsurvivor group (17.0% [31/182] vs. 13.5% [7/52], p = 0.74). A similar tendency was demonstrated for targeted combination therapy (19.8% [36/182] vs. 11.5% [6/52], respectively; p = 0.31). However, in a subgroup analysis of data from patients (n = 54) with an absolute neutrophil count less than 500/mm3, the patients who had appropriate empirical or targeted combination therapy showed better outcomes than those who underwent monotherapy or inappropriate therapy (p < 0.05). Mechanical ventilation (odds ratio [OR], 6.93; 95% confidence interval [CI], 2.64-18.11; p = 0.0001), the use of a central venous catheter (OR, 2.95; 95% CI, 1.35-6.43; p = 0.007), a high Acute Physiology and Chronic Health Evaluation II score (OR, 4.65; 95% CI, 1.95-11.04; p = 0.0001), and presence of septic shock (OR, 2.91; 95% CI, 1.33-6.38; p = 0.007) were independent risk factors for 14-day mortality. CONCLUSIONS Disease severity was a critical factor for mortality in our patients with P. aeruginosa bacteremia. Overall, combination therapy had no significant effect on 14-day mortality compared with monotherapy. However, appropriate combination therapy showed a favorable effect on survival in patients with febrile neutropenia.