Prognosis varies among persons with West Nile virus (WNV) infection, but the most important factors associated with persistent symptoms are not clear. In this cross-sectional study, 265 persons with symptomatic WNV infection during 2006–2008 completed a survey a mean of 7.7 months after diagnosis. We determined the association of demographic and clinical characteristics to the most common symptoms. Of 214 persons infected≥ 6 months, 53% reported one or more persistent symptoms, including fatigue, muscle aches, decreased activity, difficulty with memory, and difficulty concentrating. Persons with neuroinvasive disease, hypertension, or diabetes were significantly more likely to report persistent symptoms, whereas age, sex, and time since infection were not associated with persistent symptoms. In conclusion, persistent symptoms persisted in most persons for more than six months after symptomatic WNV infection. Improved strategies for prevention and treatment are needed.