BACKGROUND: We aimed to compare the characteristics of human metapneumovirus (hMPV) infection with influenza A and B virus (FLUV) and respiratory syncytial virus (RSV) infections in adults hospitalized with influenza-like illness (ILI). METHODS: We conducted a post hoc analysis of adult patients hospitalized with community-acquired ILI who were enrolled in the FLUVAC study at 5 French referral hospitals from 2012 to 2022. RESULTS: At least 1 respiratory virus was detected in 3620 of 6618 patients (55%), including FLUV (1524/3620 [42%]), RSV (248/3620 [7%]), and hMPV (162/3620 [5%]). hMPV+ patients, when compared to FLUV+ patients were more likely to develop at least 1 complication (60% [86/143] vs 50% [716/1435]; P = .02), especially acute heart failure, which occurred twice as often in hMPV+ during the hospital stay (22% [32/143] vs 11% [160/1434]; P < .001). The rates of respiratory (30% [43/143] vs 32% [70/216]; P = .73) or cardiac (22% [32/143] vs 15% [33/216]; P = .09) complications did not differ between hMPV+ and RSV+ patients. The in-hospital all-cause death rate was similar among all 3 populations (4% hMPV+, 4% FLUV+, and 5% RSV+). CONCLUSIONS: Hospitalized hMPV infections affect older patients with multiple chronic conditions who face frequent cardiac and pulmonary complications during hospitalization more frequently than with influenza and similar to RSV.