INTRODUCTION: Prolonged length of stay (pLOS) following ischemic stroke inflates cost, increases risk for hospital-acquired complications, and has been associated with worse prognosis. METHODS: Acute ischemic stroke patients admitted between July 2008 and December 2010 were retrospectively analyzed for pLOS, defined as a patient stable for discharge hospitalized for an additional ≥24 hours. RESULTS: Of 274 patients included, 106 (38.7%) had pLOS (median age 65 years, 60.6% female, 69.0% black). Patients with pLOS had higher admission NIHSS than patients without pLOS (9 versus 5, P = 0.0010). A larger proportion of patients with pLOS developed an infection (P < 0.0001), and after adjusting for covariates, these patients had greater odds of poor short-term functional outcome (OR = 2.25, 95% CI 1.17-4.32, P = 0.0148). Adjusting for infection, the odds of patients with pLOS having poor short-term functional outcome were no longer significant (OR = 1.68, 95% CI 0.83-3.35, P = 0.1443). CONCLUSIONS: The contraction of a hospital-acquired infection was a significant predictor of pLOS and a contributor of poor short-term outcome following an ischemic stroke. Whether the cause or the consequence of pLOS, hospital-acquired infections are largely preventable and a target for reducing length of stay.