Background: In moderately to severely obese patients with obstructive sleep apnea (OSA), the effects of long-term positive airway pressure (PAP) treatment on cardiovascular risk are poorly defined. Purpose: To assess the effect of continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) on the occurrence of cardiovascular events in obese OSA patients. Methods: We performed a noninterventional observational study in obese OSA patients recruited between 2007 and 2010 at the Sleep Center, University of Grenoble, treated with CPAP or NIV, and followed for 5.6 years by a single home care provider. Baseline clinical characteristics, blood chemistry, and respiratory and vascular function were assessed. Incident cardiovascular events were investigated by phone interviews. Results: A total of 103 patients (55 men, 48 women; age and body mass index [BMI] at diagnosis 54.1 ± 10.5 years and 40.3 ± 5.5, respectively [mean ± standard deviation]; CPAP: n = 75; NIV: n = 28) agreed to participate in the study. Grade I, II, and III obesity occurred in 17.5, 33.0, and 49.5% of the sample, respectively. In patients using PAP treatment (n = 69), the mean nightly use was 6.3 ± 2.4 h. Thirty-one patients stopped PAP treatment during follow-up. Three patients on NIV died. Nonfatal cardiovascular events (n = 27) occurred in 19 patients, who were older and showed higher number of comorbidities and triglyceride levels than patients without events. In the patients who interrupted treatment, the event rate was high and increased with the number of comorbidities, while BMI at baseline did not predict events. Conclusions: The study suggests that regular PAP treatment may be associated with protection against cardiovascular risk in obese OSA patients, especially in the presence of multiple comorbidities.