Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin-sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin-sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin-sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. -0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348-31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin-sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin-sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.