Background: Optimal strategies for prevention and treatment for post-stroke depression (PSD) remain unclear and a greater understanding of effect of resilience on PSD is promising. The aim was to examine the association between baseline resilience and depression at 1, 3, and 6 months after discharge, which contributes to early detection and management of PSD. Methods: A total of 217 ischemic stroke survivors were recruited in two tertiary hospitals in Shanghai, China from February 2017 to January 2018. The Chinese version of Connor-Davidson Resilience Scale (CD-RISC) was used to assess resilience at acute hospitalization. Hospital Anxiety and Depression Scale (HADS) was employed to ascertain baseline anxiety, baseline depression, and post-discharge depression. Social-demographic and disease-related information were obtained from participants’ self-report and medical records. Logistic regression analysis was used to determine which factors were independently associated with PSD. Results: The prevalence of depression at baseline was 21.2% and at 1, 3, and 6 months after discharge was 34.4%, 33.2%, and 29.2%, respectively. Logistics regression analyses indicated that resilience may independently predict PSD at 1 month (OR: 0.22, 95%CI: 0.097, 0.518), 3 months (OR:0.302, 95%CI: 0.151, 0.607), and 6 months (OR: 0.03, 95%CI: 0.006, 0.153) after controlling for social-demographics, disease-related characteristics, baseline anxiety, and baseline depression. Limitations: Non-multicenter survey and mild stroke severity may affect the generalization of these findings. Moreover, response bias should be acknowledged because some participants were read questionnaires out aloud. Conclusion: Resilience is independently associated with PSD at different timepoints. Our findings reveal the important role of resilience as a protective factor against PSD. © 2020 Elsevier B.V.