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To assess the long-term outcomes of patients hospitalized with severe West Nile neuroinvasive disease.Retrospective cohort.Patients admitted to a referral center (Saint Mary’s Hospital, Mayo Clinic).Twenty-six patients with West Nile neuroinvasive disease were identified by retrospective search of electronic database of Saint Mary’s Hospital from January 1999 to November 2016.Retrospective electronic medical records review and prospective telephone follow-up.Functional disability and cognitive outcomes were evaluated with the modified Rankin Scale and the Telephone Interview for Cognitive Status scores. Data on the time that the patient returned home after the hospitalization for West Nile neuroinvasive disease and the time of return to work were also collected. We identified 26 patients (81% males), 59 ± 17 years old. After a median hospital stay of 14.5 days (3–126), four patients died and 90% of survivors had a modified Rankin Scale of 3–5. Two additional patients died, and 80% of survivors had a modified Rankin Scale of 0–2 after a median follow-up of 73 months (1–144). Seven patients had cognitive impairment, which was severe in two of them. The combination of encephalitis and acute flaccid paralysis at presentation was associated with lower likelihood of returning home within 1 month after discharge (p < 0.01). Patients who required mechanical ventilation were more likely to have a modified Rankin Scale of 3–5 at last follow-up (p = 0.03), less likely to return home within 1 month of discharge (p < 0.01), less likely to return to their jobs (p < 0.01), and showed a trend toward having cognitive impairment (p = 0.05).Despite having poor outcomes at discharge, most West Nile neuroinvasive disease survivors with severe early disability can recover functional independence in the long term, justifying aggressive support during the acute phase and extensive rehabilitation efforts.