Abstract Background There are no clinical outcome assessment (COA) tools developed in accordance with Food and Drug Administration (FDA) guidance suitable for the evaluation of symptoms associated with respiratory syncytial virus (RSV) infection among infants. The Gilead RSV Caregiver Diary (GRCD) is being developed to fulfill this need; the present research evaluates the GRCD and documents its reliability, validity, and responsiveness among children < 24 months of age with acute RSV infection. Methods A prospective, observational study was conducted in the United States during the 2014–2015 northern hemisphere winter season. Subjects were < 24-month, full-term, previously healthy infants with confirmed RSV infection and ≤5 days of symptoms. The GRCD was completed twice daily for 14 days by caregivers. Additional data were collected during the initial visit, subsequent visits, and end-of-study interview. Test-retest reliability (kappa and intraclass correlation coefficients [ICCs]), construct validity (correl...