OBJECTIVES: To assess the cost-effectiveness of linezolid versus vancomycin in the treatment of NP in four major cities (Beijing, Guangzhou, Nanjing, and Xi’an) in China. METHODS: We conducted cost-effectiveness analyses from Chinese payers’ perspective piggybacked to a phase IV, randomized, double-blind, multicenter study (Wunderink et al, CID 2012) in MRSA-NP patients (microbiologic confirmed intent-to-treat cohort). Efficacy was measured by treatment success (defined as Cure+Improvement) at the end of study (i.e., 7-30 days after the end of treatment). Direct medical costs from four cities in China (¥, 2012) were calculated from the healthcare resource use data collected from the trial, including study medication, hospitalization, mechanical ventilation, and continuous renal replacement therapy. Nonparametric bootstrapping method was used to calculate confidence intervals (CI) for costs, efficacy, and incremental cost-effectiveness ratios (ICER). RESULTS: Data from 391 patients (186 linezolid, 205 vancomycin) were analyzed. More linezolid patients achieved treatment success vs. vancomycin patients [mean (95% CI)]: 55% (48.3%-61.9%) vs. 45% (38%-52.3%). The total treatment costs of linezolid vs. vancomycin were: ¥79,551(¥72,421-¥86,680) vs. ¥77,587(¥70,656-¥84,519) for Beijing, ¥90,995(¥82,598-¥99,393) vs. ¥89,448(¥81,295-¥97,601) for Guangzhou, ¥82,383(¥74,956-¥89,810) vs. ¥80,799(¥73,545-¥88,054) for Nanjing, and ¥59,413(¥54,366-¥64,460) vs. ¥57,804(¥52,613-¥62,996) for Xi’an. The ICER of linezolid over vancomycin were ¥19,719(-¥143,553-¥320,980), ¥15,532(-¥185,411-¥349,693), ¥15,904(-¥161,935-¥314,987), and ¥16,145(-¥100,738-¥234,412) per additional treatment success for Beijing, Guangzhou, Nanjing, and Xi’an, respectively. Out of 10,000 bootstrap simulations, majority cases had greater efficacies and higher costs for linezolid (in quadrant I of the DE-DC plane: Beijing(64%), Guangzhou(59%), Nanjing(61%), Xi’an(66%)), more than one third had greater efficacies and lower costs for linezolid (linezolid dominated vancomycin: Beijing(33%), Guangzhou(38%), Nanjing(37%), Xi’an(32%)); only <2% had greater efficacies and lower costs for vancomycin in all cities (vancomycin dominated linezolid). CONCLUSIONS: In this clinical trial population, linezolid appears to be cost-effective from Chinese payers’ perspective when compared to vancomycin in treating patients with nosocomial pneumonia caused by MRSA.