Objective: To understand the antiretroviral treatment (ART) discontinuation rate and its influencing factors among HIV infected patients who initiated ART between 2012 and 2015 in Wenshan prefecture, Yunnan province. Methods: Demographic characteristics, baseline informations of ART, initial treatment regimens and follow-up status of a total of 4 354 patients who initiated ART from 2012 to 2015 in Wenshan prefecture were collected. A historical cohort study was used to describe the discontinuation incidence rate of ART. Life table was used to estimate cumulative retention rate and Cox proportional hazard model was used to determine the influencing factors of ART discontinuation. Results: The percentage and incidence rate of discontinuation were 25.1% (1 092/4 354) and 14.53 per 100 person-years among patients who initiated ART from 2012 to 2015 in Wenshan prefecture. ART retention rates were 88%, 83%, 78%, 74% at 6^th month, 12^th month, 18^th month, 24^th month, respectively. The multivariate Cox proportional hazard regression model showed that male patients were at a higher risk of discontinuation (HR=1.24, 95%CI: 1.09-1.41) than female patients, patients aged ≥50 years were at a higher risk of discontinuation (HR=1.27, 95%CI: 1.06-1.53) than patients aged<30 years, discontinuation hazard among patients who were unmarried or divorced or widowed was 1.30 times (HR:1.30, 95%CI: 1.14-1.48) as patients who were married or cohabitation, discontinuation hazard among patients infected with HIV through injection drug use (IDU) was 1.49 times (HR:1.49, 95%CI: 1.23-1.82) as those infected through heterosexual transmission, patients with a baseline CD4 cell count<350/μl (HR=1.34, 95%CI: 1.13-1.58) or ≥500/μl (HR=1.36, 95%CI: 1.09-1.71) were at a higher risk of discontinuation than those with a baseline CD4 cell count from 350/μl to 500/μl, patients initiating ART in 2014 (HR=1.25, 95%CI: 1.04-1.50) or in 2015 (HR=1.26, 95%CI: 1.02-1.55) were at a higher risk of discontinuation than those initiating ART in 2012. Conclusion There is an uptrend for ART discontinuation rate in Wenshan prefecture. Male, 50 years or older, unmarried or divorced or widowed, transmission route as IDU, baseline CD4 count <350/μl or ≥500/μl are risk factors of ART discontinuation.