To prospectively evaluate the long-term impact of Kawasaki disease (KD) hospitalization on health-related quality of life (HRQoL). We merged the Outcomes Assessment Program and KD databases and queried for KD admissions between 1 month and 18 years of age. Patients with a diagnosis of community-acquired pneumonia were included as a comparison group. HRQoL was evaluated with the parent proxy Pediatric Quality of Life Inventory (PedsQL). Long-term follow-up PedsQL surveys were performed at least 1 year after initial diagnosis and hospitalization. Results for the entire cohort adjusted for significant differences were calculated. Propensity score-matched cohorts were constructed from the unmatched cohorts of patients with long-term survey responses. Subgroup analysis for the KD group was performed. Patients with KD (n = 61) versus pneumonia (n = 80) had a lower PedsQL total score on admission and experienced a significantly greater HRQoL decline from baseline to admission. At long-term follow-up, no difference occurred in HRQoL between patients with KD and pneumonia, and 89% of patients with KD reached their baseline PedsQL scores. KD diagnostic subtype, coronary artery dilatation, and need for longer follow-up were not associated with HRQoL outcomes at any time point. Intravenous immunoglobulin nonresponders demonstrated lower HRQoL at admission, which did not persist at follow-up. Children with KD experience acute and significant HRQoL impairment exceeding that of children with newly diagnosed pneumonia, but the scores return to baseline at long-term follow-up. The recoveries at short- and long-term intervals are similar to patients with pneumonia.