The objective of this study was to investigate the prevalence of drug-resistant Helicobacter pylori in Beijing Tian Tan Hospital (Beijing, China) and to determine the susceptibility of H. pylori to linezolid and novel oxazolidinone analogues. Minimum inhibitory concentrations (MICs) of amoxicillin, clarithromycin, metronidazole, ciprofloxacin, tetracycline and levofloxacin against H. pylori were determined by Etest. The in vitro antibacterial activities of linezolid and novel oxazolidinone analogues were assessed by the disk diffusion method. In vivo antibacterial activities were determined by intragastric administration and stomach CFU counting. Drug resistance patterns were serious among clinical H. pylori isolates, with a rate of multidrug-resistant H. pylori of 10.1%. Linezolid was observed to exhibit in vitro activity, with MICs ranging from <= 0.25 mg/L to 32 mg/L against clinical H. pylori isolates (MIC50, 2 mg/L; MIC90, 8 mg/L). The oxazolidinone analogue sy142 demonstrated better antimicrobial activity than linezolid in vitro. These results indicate that oxazolidinones may be appropriate agents to treat drug-resistant H. pylori. Further clinical trials should be performed to confirm this. (C) 2016 Published by Elsevier Ltd on behalf of International Society for Chemotherapy of Infection and Cancer.