Rationale: Epidemiologic studies on the consequences of sleep-disordered breathing (SDB) invariably use the apnea-hypopnea index as the primary measure of disease severity. Although hypopneas constitute a majority of disordered breathing events, significant controversy remains about the best criteria used to define these events. Objectives: The current investigation sought to assess the most appropriate definition for hypopneas that would be best correlated with cardiovascular disease in a community sample of middle aged and older adults. Full-montage polysomnography was conducted and hypopneas were defined based on different oxyhemoglobin desaturation thresholds with and without arousals. Results: Using a sample of 6,106 adults participating in the Sleep Heart Health Study with complete data on cardiovascular disease status and polysomnography, the current study found that hypopneas associated with an oxyhemoglobin desaturation of 4% or more were associated with prevalent cardiovascular disease independent of confounding covariates. The adjusted prevalent odds ratios for quartiles of the hypopnea index using a 4% desaturation criterion were as follows: 1.00 (<1.10 events/hr), 1.10 (1.01-3.20 events/hr), 1.33 (3.21-7.69 events/hr), and 1.41 (>7.69 events/hr). Hypopnea measures based on less than 4% oxyhemoglobin desaturation or presence of arousals showed no association with cardiovascular disease. Conclusions: Hypopneas comprise a significant component of SDB in the general community. By varying the criteria for defining hypopneas, this study demonstrates that hypopneas with a desaturation of at least 4% are independently associated with cardiovascular disease. In contrast, no association was observed between cardiovascular disease and hypopneas associated with milder desaturations or arousals.