ABSTRACT: BACKGROUND:Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. METHODS:Using the Veterans Aging Cohort Study Survey Cohort, insomnia symptoms were measured and dummy coded with the item, "Difficulty falling or staying asleep?" (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with the Department of Veterans Affairs (VA) and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. RESULTS:HIV-infected (N = 3108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics [hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.16 to 2.31, P = 0.005], CVD risk factors (HR = 1.62, 95% CI: 1.14 to 2.30, P = 0.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, and cocaine use; HR = 1.70, 95% CI: 1.19 to 2.43, P = 0.003), and HIV-specific factors (HIV-1 RNA, CD4 T-cell count, and antiretroviral therapy; HR = 1.66, 95% CI: 1.16 to 2.37, P = 0.005). Additional adjustment for nonbenzodiazepine sleep medication (HR = 1.62, 95% CI: 1.13 to 2.32, P = 0.009) did not attenuate the association; however, it fell short of significance at P < 0.01 after adjustment for depressive symptoms (HR = 1.51, 95% CI: 0.98 to 2.32, P = 0.060) or antidepressant medication (HR = 1.51, 95% CI: 1.04 to 2.19, P = 0.031). CONCLUSIONS:Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV.