Objective: To ascertain whether objectively measured obstructive sleep apnea (OSA) independently increases the risk of all cause death, cardiovascular disease (CVD), coronary heart disease (CHD), stroke or cancer Design: Community-based cohort Setting and Participants: 400 residents of the Western Australian town of Busselton Measures: OSA severity was quantified via the respiratory disturbance index (RDI) as measured by a single night recording in November-December 1990 using the MESAM IV device, along with a range of other risk factors. Follow-up for deaths and hospitalizations was ascertained via record linkage to the end of 2010. Results: We had follow-up data in 397 people and then removed those with a previous stroke (n = 4) from the mortality/CVD/CHD/stroke analyses and those with cancer history from the cancer analyses (n = 7). There were 77 deaths, 103 cardiovascular events (31 strokes, 59 CHD) and 125 incident cases of cancer (39 cancer fatalities) during 20 years follow-up. In fully adjusted models, moderate-severe OSA was significantly associated with all-cause mortality (HR = 4.2; 95% CI 1.9, 9.2), cancer mortality (3.4; 1.1, 10.2), incident cancer (2.5; 1.2, 5.0), and stroke (3.7; 1.2, 11.8), but not significantly with CVD (1.9; 0.75, 4.6) or CHD incidence (1.1; 0.24, 4.6). Mild sleep apnea was associated with a halving in mortality (0.5; 0.27, 0.99), but no other outcome, after control for leading risk factors. Conclusions: Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality, incident stroke, and cancer incidence and mortality in this community-based sample.