ObjectiveTo examine whether baseline depression predicts subsequent peptic ulcer disease (PUD) in older people living alone and whether social engagement plays a role in such an association. MethodsBetween May 2010 and May 2015, 2, 850 older people living alone were recruited from eight Grade-A hospitals in the People's Republic of China and followed for up to 36 months. The Kaplan–Meier method was used to investigate how the incidence of PUD varied with depression and social engagement status. Multivariate Cox proportional hazards models were estimated to examine the association between depression and incidence of PUD and assess the role of social engagement in this relationship. ResultsKaplan–Meier curves indicated that the 36-month cumulative incidence of PUD was higher in depressed (10.1%) than non-depressed participants (5.3%). However, among the depressed participants, increased or continued social engagement reduced the incidence to 6.2% and 7.9%, respectively. Multivariate analyses showed that baseline depression was associated with subsequent PUD development (hazard ratio [HR] = 2.520, 95% confidence interval [CI]: 1.525–3.356). The incidence of PUD was similar in non-depressed and depressed participants who reported increased (HR = 1.956, 95% CI: 0.913–3.374) or continued social engagement (HR = 1.827, 95% CI: 0.918–3.690) during the follow-up period. However, depressed participants who reported decreased (HR = 2.485, 95% CI: 1.459–3.295) or no social engagement (HR = 2.896, 95% CI: 1.817–4.228) were more likely to develop PUD than those without depression. ConclusionsBaseline depression was associated with subsequent incidence of PUD, but this association appears to be reduced by increased or continued social engagement.