Background: The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma). Methods: This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017–2019). The RiiQ™ Symptom Scale and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post-discharge. Results: Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post-discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post-discharge. Participants with CRF reported more moderate-to-severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(−) participants post-discharge. EQ-5D-5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains. Conclusions: Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ-5D-5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies.