Background: Ischemic preconditioning, whereby transient ischemic episodes induce endogenous cardioprotective responses to enhance tolerance of the heart to sustained ischemia/reperfusion injury, is reproducibly demonstrated in animal models, but clinical correlation in humans is not well established.Hypothesis: Episodic hypoxemia in obstructive sleep apnea (OSA) may precondition the heart to injury increasing tolerance to acute myocardial infarction (AMI) compared to non-OSA patients, resulting in improved in-hospital survival.Methods: Using the Nationwide Inpatient Sample database, all patients hospitalized with AMI in 2012 were identified. OSA (ICD-9 code 327.23) was 1:1 propensity score matched (age, sex, BMI and major comorbidities) with no OSA group. Baseline characteristics and clinical outcomes between the two groups were compared using Wilcoxon, T-test and Chi square test. Logistic regression model was used to identify independent predictors of mortality.Results: Out of 188,950 patients (mean age 69 ± 14yrs, 69% male) who experienced AMI, 5.4% had OSA and 1:1 matched with non-OSA patients with AMI. In the unmatched cohort the overall in-patient mortality in the OSA group was significantly lower than those with non-OSA [5.9% vs 8.8%; OR=0.64 (95% CI 0.59, 0.70); p<0.001] and this difference persisted even after propensity matching for baseline differences with in hospital mortality 4.4% vs 5.7% [OR=0.74; (95% CI 0.63, 0.86); p<0.001], respectively. In addition to OSA, hyperlipidemia was protective, while age, history of heart failure, renal failure, stroke and severe sepsis were independent risk factors of poor mortality. (Figure)Conclusions: Patients with OSA compared to non-OSA had lower in-hospital mortality after AMI that was independent of age and comorbidities, suggesting that OSA has a protective effect against AMI thus providing support for hypoxemic preconditioning in humans.