Linezolid (LZD) serves as an effective option in the treatment of Mycobacterium abscessus complex (MABC) infection. Unfortunately, the combined activities of LZD with other antimicrobial agents against MABC have not been evaluated systemically. In this study, we randomly selected 32 Mycobacterium abscessus and 32 Mycobacterium massiliense isolates for the determination of in vitro synergistic effect between LZD and other antimicrobial agents, including amikacin (AMK), moxifloxacin (MOX), cefoxitin (CFX) and tigecycline (TGC). Out of 64 MABC isolates tested, only one (1.6%, 1/64) and two (3.2%, 2/64) exhibited resistance to AMK and LZD, respectively. Statistical analysis revealed that the percentage of TGC-resistant isolates was significantly lower among M. massiliense (9.4%, 3/32) than that among M. abscessus (25.0%, 8/32, P < 0.001). In addition, LZD and AMK showed synergy for 29 MABC isolates (453%), whereas no antagonism was noted for this combination. The second mostly frequent synergistic effect was found in LZD plus TGC combination, and 26.6% (17/64) of the strains tested exhibited synergy. In contrast, LZD-CFX and LZD-MOX combinations appeared antagonistic for half of the isolates (48.4%, 31/64 for CFX and 51.6%, 33/64), and almost no synergistic effect was reported in any of the strains for these two combinations. In conclusion, our data reveal that LZD and AMK show the most potent activity against MABC. The frequent synergism is observed in LZD-AMK and LZD-TGC combinations, while LZD rarely exhibits in vitro synergy with MOX and CFX when tested against MABC. (C) 2017 Elsevier Inc. All rights reserved.