OBJECTIVE： To control the risk of off-label drug use，and to provide reference for rational drug use. METHODS： Outpatient prescriptions were selected by stratified equal proportion sampling method from a third grade class A hospital during Jun. 2015-Jun. 2016. According to the latest edition of drug instruction issued by CFDA， the off-label prescriptions were screened and analyzed statistically. According to Micromedex tools and literatures report， guidelines， off-label drug use and related severe ADR were analyzed. RESULTS： Of 3 025 outpatient prescriptions， 11.2％ of prescriptions （339 pieces） were considered as off-label prescriptions， including without indication （88.7％）， over dose （6.0％）， beyond route of administration （3.2％） and beyond adapt-to-the-crowd （2.1％）. Gastroesophagedal reflux was the main diagosis （16.0％）. 1.5％ of off-label drug use were supported by FDA-approved labels， 83.8％ of them were supported by international and national guidelines， 12.4％ of them were supported by expert consensus， and 2.4％ of them were supported by other literature report. Thirteen items of off-label drug use had been included in Micromedex， recommendation grade and evidence intensity of which varied. Eight drugs of off-label drug use were reported to result in serious ADR. CONCLUSIONS： All off-label drug use in outpatient department of this hospital is supported by evidence-based medical evidence. But the quality of evidence varies. In the practice， physicians and pharmacists should balance the benefit and risk of off-labed drug use carefully.