Objective: To assess the effect of time to acute therapy on health-related quality of life (HRQoL) and disability after ischemic stroke. Design: Prospective cohort study. Setting: Comprehensive stroke care center in a large metropolitan city. Participants: Patients (N=553; mean age, 67 y; 51.9% male; 64.4% white; 88.8% ischemic stroke) with ischemic stroke or transient ischemic attack (TIA) enrolled in a longitudinal observational study between August 2012 to January 2014 who received rehabilitation services. Intervention: Not applicable. Main Outcome Measures: Disability status was assessed with the modified Rankin Scale (mRS) and Barthel Index (BI). HRQoL was assessed using the Quality of Life in Neurological Disorders measures of executive function, general cognitive concerns, upper extremity dexterity, and lower extremity mobility. Time to therapy consult and treatment were defined as the number of days from hospital admission to initial consult by a therapist and number of days from hospital admission to initial treatment, respectively. Results: Among the participants, the median number of days from hospital admission to acute therapy consult was 2 days (interquartile range, 1-3d). Multivariable linear and logistic regression models indicated that for those with the National Institutes of Health Stroke Scale (NIHSS) score<5, longer time to therapy consult was associated with worse BI scores (BI=100; odds ratio [OR], 0.818; P=.008), executive function T scores (b=–0.865; P=.001), and general cognitive concerns T scores (b=–0.609; P=.009) at 1-month in adjusted analyses. In those with NIHSS score≥5, longer time to therapy treatment led to increased disability (ie, mRS≥ 2; OR, 1.15; P=.039) and lower extremity mobility T scores (b=–0.591; P=.046) at 1 month in adjusted analyses. Conclusions: Longer time to initiation of acute therapy has differential effects on poststroke disability and HRQoL up to 1-month after ischemic stroke and TIA. The effect of acute therapy consult is more notable for those with mild deficits, while the effect of acute therapy treatment is more notable for those with moderate to severe deficits. Minimizing time to therapy consults and treatments in the acute hospital period might improve outcomes after ischemic stroke and TIA.