BackgroundChina has ambitious to achieve significant reductions in HIV transmission and HIV-related mortality by adopting the World Health Organization's “Treat All” approach. Such a prevention strategy is needed future study on regional scale.MethodsAn observational cohort study of HIV epidemiology and treatment databases was used to study the effectiveness of antiretroviral therapy on the transmission of HIV in serodiscordant couples in Guangxi of China.ResultsA total of 7713 couples were entered into the cohort study analysis which included 1885 couples in the treatment-naive cohort and 5828 couples in the treated cohort. During the follow-up of 18985.29 person-years from 2003 to 2014, the average incidence of HIV was 2.4 per 100 person-years (95% CI 2.1–2.6). HIV seroincidence rate was significantly higher among the treatment naive group (4.2 per 100 person-years, 3.7–4.8) compared with the on treatment group (1.6 per 100 person-years, 1.3–1.8). An overall 45% reduction in risk of HIV transmission among serodiscordant couple was associated with ART treatment (adjusted Hazard Ratio [HR] 0.55, 95% Confidence Interval [CI] 0.44–0.69). Treatment prevention had significantly effectiveness for most baseline characteristics of index partners, such as for male, female, age above 25 years, education below high school, farmer, infected by heterosexual intercourse.ConclusionTreatment-as-prevention can be implemented in the real-world on a national or regional scale, but ART adherence and comprehensive harm reduction while implementing this strategy require further study.