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Mental illness and obesity are highly prevalent in patients with coronary disease and are frequently comorbid. While mental illness is an established risk factor for major adverse cardiac and cerebrovascular events (MACCEs), prior studies suggest improved outcomes in people with obesity. It is unknown if obesity and mental illness interact to affect cardiac outcomes or if they independently influence MACCE. We identified 55 091 patients undergoing percutaneous coronary intervention (PCI) between 2009 and 2014, using the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking (CART) program. Cox methods were used to assess the risk of MACCE by weight status and psychiatric diagnosis, and assessed for interaction. Compared to normal weight status, higher weight was associated with reduced MACCE events after PCI (mean follow-up of 2 years) for both stable angina and acute coronary syndromes (ACSs; reduction of >13% in stable angina, >17% in ACS; P < 0.01 for both after adjustment). Having a non-substance abuse mental illness diagnosis increased risk of MACCE compared to patients without mental illness in stable angina over 17%; P < 0.05, but not in ACS. When analysed for interaction, obesity and mental illness did not significantly impact MACCE over their independent influences. These results suggest that mental illness along with weight status have significant impact on MACCE, post-PCI. Clinicians should be aware of patients' mental health status as a significant cardiovascular risk factor after PCI, independent of weight status., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)