Background-Obstructive sleep apnea (OSA) is an important risk factor for the development of cardiovascular diseases including myocardial infarction (MI). The aim of this study was to investigate the effects of OSA on prognosis after MI, and to determine which specific measures of OSA severity best predicted outcomes. Methods and Results-We performed a prospective study, in which 112 patients without a prior diagnosis of sleep apnea underwent comprehensive polysomnography within a median of 7 days after MI. Patients were followed up at 6-monthly intervals (+/- 2 weeks) for a total of 48 months. Patients classified with central apnea (n=6) or those using continuous positive airway pressure (n=8) after polysomnography were excluded from analyses. The primary end point was major adverse cardiac events, including death from any cause, recurrent MI, unstable angina, heart failure, stroke, and significant arrhythmic events. Forty of 98 patients (41%) had OSA (apnea-hypopnea index >= 15 events/h). OSA patients had higher major adverse cardiac event rates when compared to those without OSA (47.5% versus 24.1%; chi(2)=5.41, P=0.020). In a multivariate model that adjusted for clinically relevant variables including age, left ventricular ejection fraction, diabetes mellitus, oxygen desaturation index, and arousal index, significant hypoxemia, as defined by nocturnal nadir oxygen saturation <= 85%, was an independent risk factor for major adverse cardiac events (hazard ratio=6.05, P=0.004) in follow-up 15 months after baseline. Conclusions-Nocturnal hypoxemia in OSA is an important predictor of poor prognosis for patients after MI. These findings suggest that routine use of low-cost nocturnal oximetry may be an economical and practical approach to stratify risk in post-MI patients.