ABSTRACT / PROJECT SUMMARY We propose the “Targeting cardiovascular events to improve patient outcomes after sepsis” study to identify opportunities to improve long-term patient outcomes after sepsis through the discovery of novel, potentially modifiable, risk factors for post-sepsis cardiovascular events. Sepsis is a life-threatening, dysregulated response to infection and the most common illness leading to hospitalization in the United States, affecting ~1 million Americans yearly. Cardiovascular complications are among the most common reasons for morbidity, re- hospitalization and death after sepsis. Approximately 1 in 3 sepsis survivors are hospitalized for cardiovascular events in the year following sepsis. Cardiovascular complications after sepsis are common, but the risk factors are undefined and likely differ from traditional cardiac risk factors. In addition, prescribing patterns of potentially cardio-protective medications are unclear and effectiveness of traditional cardiovascular risk-modifying treatments after sepsis are uncertain. We propose to use longitudinal, granular, electronic health record data across multiple centers to address knowledge gaps involving predictors of cardiovascular complications, practice patterns of cardiovascular risk modification, and effectiveness of therapies prescribed to reduce cardiovascular risk in the especially vulnerable period after sepsis. We have assembled a team with expertise in using longitudinal electronic health record data to study novel cardiovascular risk factors and sepsis with state-of-the-art methods. Results from our study will provide new insights into the common intersection of sepsis with cardiovascular events and will inform current therapeutic strategies, as well as the conduct of future randomized trials investigating novel methods to reduce cardiovascular complications and improve patient outcome after sepsis.