BACKGROUND: Obstructive sleep apnea (OSA) has been associated with clinical deterioration in postoperative patients and patients hospitalized with pneumonia. Paradoxically, OSA has also been associated with decreased risk of inpatient mortality in these same populations. OBJECTIVES: To investigate the association between OSA and in-hospital mortality in a large cohort of surgical and nonsurgical ward patients. DESIGN: Observational cohort study. SETTING: A 500-bed academic tertiary care hospital in the United States. PATIENTS: A total of 93,676 ward admissions from 53,150 unique adult patients between November 1, 2008 and October 1, 2013. INTERVENTION: None. MEASUREMENTS: OSA diagnoses and comorbidities were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Logistic regression was used to control for patient characteristics, location prior to ward admission, and admission severity of illness. The primary outcome was in-hospital death. Secondary outcomes included rapid response team (RRT) activation, intensive care unit (ICU) transfer, intubation, and cardiac arrest on the wards. MAIN RESULTS: OSA was identified in 5,625 (10.6%) patients. Patients with OSA were more likely to be older, male, and obese, and had higher rates of comorbidities. OSA patients had more frequent RRT activations (1.5% vs 1.1%) and ICU transfers (8% vs 7%) than controls (P < 0.001 for both comparisons), but a lower inpatient mortality rate (1.1% vs 1.4%, P < 0.05). OSA was associated with decreased adjusted odds for ICU transfer (odds ratio [OR]: 0.91 [0.84-0.99]), cardiac arrest (OR: 0.72 [0.55-0.95]), and in-hospital mortality (OR: 0.70 [0.58-0.85]). CONCLUSIONS: After adjustment for important confounders, OSA was not associated with clinical deterioration on the wards and was associated with significantly decreased in-hospital mortality.