Most mortality associated with West Nile virus (WNV) disease occurs during the acute or early convalescent phases of illness. However, some reports suggest mortality may be elevated for months or longer after acute illness. The objective of this study was to assess the survival of a cohort of patients hospitalized with WNV disease in Colorado in 2003 up to 4 years after illness onset. We calculated age-adjusted standardized mortality ratios (SMRs) to evaluate excess mortality, evaluated reported causes of death in those who died, and analyzed potential covariates of delayed mortality. By 1 year after illness onset, 4% of the 201 patients had died (SMR, 2.7; 95% confidence interval [CI], 1.3-5.2), and 12% had died by 4 years after onset (SMR, 2.0; 95% CI, 1.3-3.0). Among those who had died, the most common immediate and contributory causes of death included pulmonary disease and cardiovascular disease; cancer, hepatic disease, and renal disease were mentioned less frequently. In multivariate analysis, age (hazard ratio [HR], 2.0 per 10-year increase; 95% CI, 1.4-2.7), autoimmune disease (HR, 3.0; 95% CI, 1.1-7.9), ever-use of tobacco (HR, 3.0; 95% CI, 1.3-7.0), encephalitis during acute WNV illness (HR, 2.6; 95% CI, 1.1-6.4), and endotracheal intubation during acute illness (HR 4.8; 95% CI, 1.9-12.1) were found to be independently associated with mortality. Our finding of an approximate twofold increase in mortality for up to 3 years after acute illness reinforces the need for prevention measures against WNV infection among at-risk groups to reduce acute as well as longer-term adverse outcomes.