The aim of this study was to investigate the in vitro activity of minocycline combined with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii (CRAB). A total of 53 nonduplicate CRAB were collected from inpatients of intensive care units in three hospitals in China from February 2009 to August 2011. Minimum inhibitory concentrations were determined by the broth microdilution method. The checkerboard method was used to determine whether combinations of the two agents act synergistically. Among the 53 A. baumannii, 64.2% of the isolates were susceptible to amikacin and 69.8% were susceptible to cefoperazone-sulbactam. More than 80% of isolates were resistant to the other agents and no isolates were found resistant to polymyxin B and minocycline. The combination of minocycline and cefoperazone-sulbactam demonstrated synergism in 39 isolates, partial synergism in 11 isolates, and indifference in 3 isolates. No antagonistic interactions were observed. Our study demonstrated that minocycline has good activity against CRAB and the combination of minocycline with cefoperazone-sulbactam had significant synergistic activity against these strains in vitro. The combination of minocycline and cefoperazone-sulbactam may be an alternative option for the treatment of infections caused by CRAB.