The increased incidence of multidrug-resistant (MDR) Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients poses a severe therapeutic problem. The aim of this study was to evaluate the efficacy and safety of 2 high-dose treatment regimens of ampicillin-sulbactam (A/S) for MDR Acinetobacter baumannii VAP. We undertook a randomized, prospective trial of critically ill patents with (MDR) Acinetobacter baumannii VAP. Patients were randomly assigned to 1 of 2 treatment regimens of A/S (at a rate 2:1 every 8 h): 1) group A, 18/9 g daily dose (n = 14); and 2) group B, 24/12 g daily dose (n = 13). The duration of therapy was 8+/-2 d for both groups. A total of 27 patients were enrolled in the study. Clinical improvement was seen in 66.7% of the study population in 9/14 (64.3%) of group A patients and 9/13 (69.2%) of group B patients, respectively. Bacteriological success was achieved in 77.8% of the study population (12/14, 85.7% of group A) and in 9/13 (69.2%) of group B patients. The 14-d mortality rate was 25.9% and the all cause 30-d mortality was 48.1%. Both mortality rates did not differ significantly between the 2 groups. No major adverse reactions were recorded. We concluded that clinical and bacteriological results of the study support the use of high-dose regimen of ampicillin-sulbactam for MDR Acinetobacter baumannii VAP.