Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for depression but there is a concern about the risk of upper gastrointestinal bleeding (UGIB). Past studies, however, are largely confounded by the presence of Helicobacter pylori (HP).To evaluate the UGIB risk of SSRI users after treatment for HP.This was a propensity score (PS) matched cohort study with patients who used SSRI after receiving HP eradication therapy from the Hong Kong territory-wide healthcare database. The primary outcome was hospitalisation for nonvariceal UGIB. PS matching analysis with a ratio of 1:2 plus Cox regression model was used to compute the hazards ratios (HR) and 95% CI of UGIB risk.In this study, 3358 SSRI users and 57 906 non-users were included. The median follow-up duration was 7.74 (interquartile range 5.32-10.42) years. The crude incidence of hospitalisation for UGIB was 3.98 (95% CI 3.80-4.16) per 1000 person-years. In the PS matching analysis of 3358 SSRI users with 6716 non-users, SSRI was associated with a higher risk of UGIB compared to non-users (HR 1.95, 95% CI 1.41-2.70). This result was consistent in sensitivity analysis with 1:1 PS matching (HR 2.13, 95% CI 1.50-3.02) and multivariable analysis with 1-month intervals (HR 1.81, 95% CI 1.34-2.45) or 3-month intervals (HR 1.61, 95% CI 1.20-2.17). After stratifying by age, the increased risk of SSRI was only significant among patients >50 years.SSRI users have a higher risk of hospitalisation for nonvariceal UGIB after treatment for HP, particularly among older patients.