Objectives: To determine the prevalence and risk factors associated with depression of outpatients in three general hospitals in southern China.Methods: This hospital-based, cross-sectional descriptive study was conducted in outpatient departments of Neurology, Gastroenterology, Cardiology and Gynaecology of three general hospitals between March and June 2016. A total of 5294 adult respondents (≥18 years) in clinic waiting rooms were recruited, and 4976 were eligible to participate in the study. The nine-item Patient Health Questionnare-9 (PHQ-9) Scale was used to assess the presence of depressive symptoms. Binary logistic regression analysis was performed to identify the risk factors associated with depressive symptoms.Results: The prevalence of depressive symptoms among outpatients was 26.0% (95% CI: 24.8-27.3%). Risk factors associated with depressive symptoms included younger age (OR = 0.960; 95% CI: 0.95-0.971), social alcohol drinking (OR = 1.339; 95% CI: 1.074-1.668) and sleep disturbance (OR = 3.678; 95% CI: 3.025-4.471).Conclusions: This study provides evidence that depressive symptoms are prevalent among outpatients of general hospitals. Moreover, younger age, alcohol consumption and sleep disturbance may potentially be useful for targeted screening and prevention for outpatients with depression seen in general hospitals.KeypointsThe prevalence of self-reported depressive symptoms is common in outpatients in clinical settings.Younger age, current alcohol drinking and sleep disturbance are the associated risk factors for depression in outpatient population.Alcohol prevention and sleep quality improvement need to be incorporated into strategies aimed at the prevention and management of depression.