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Cardiac surgery is a high-risk procedure performed by a multidisciplinary team using complex tools and technologies. Efforts to improve cardiac surgery safety have been ongoing for more than a decade, yet the literature provides little guidance regarding best practices for identifying errors and improving patient safety. This focused review of the literature was undertaken as part of the FOCUS initiative (Flawless Operative Cardiovascular Unified Systems), a multifaceted effort supported by the Society of Cardiovascular Anesthesiologists Foundation to identify hazards and develop evidence-based protocols to improve cardiac surgery safety. Hazards were defined as anything that posed a potential or real risk to the patient, including errors, near misses, and adverse events. Of the 1438 articles identified for title review, 390 underwent full abstract screening, and 69 underwent full article review, which in turn yielded 55 meeting the inclusion criteria for this review. Two key themes emerged. First, studies were predominantly reactive (responding to an event or report) instead of proactive (using prospective designs such as self-assessments and external reviewers, etc.) and very few tested interventions. Second, minor events were predictive of major problems: multiple, often minor, deviations from normal procedures caused a cascade effect, resulting in major distractions that ultimately led to major events. This review fills an important gap in the literature on cardiac surgery safety, that of systematically identifying and categorizing known hazards according to their primary systemic contributor (or contributors). We conclude with recommendations for improving patient outcomes by building a culture of safety, promoting transparency, standardizing training, increasing teamwork, and monitoring performance. Finally, there is an urgent need for studies that evaluate interventions to mitigate the inherent risks of cardiac surgery.