Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015). In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen’s κ statistics. Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs. Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI. NCT01995175.