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Human metapneumovirus (hMPV) causes mild and self-limiting disease in adults. However, the risk factors for serious adverse outcomes following hMPV infection in adult patients without preexisting chronic airway diseases remain poorly understood. We conducted a territory-wide retrospective study on adult patients (aged ≥ 18 years) without chronic airway diseases hospitalized for hMPV infections between January 1, 2016 and June 30, 2023 in Hong Kong. We assessed the incidence and risk factors for in-patient mortality, severe respiratory failure (SRF), secondary bacterial pneumonia and acute kidney injury (AKI) were assessed. A total of 1552 eligible adult patients without chronic airway diseases hospitalized for hMPV infections were analyzed. Within the index admission, 92 (5.9%) patients died. Ischemic heart disease (IHD) was associated with increased risks of SRF [adjusted odds ratio (aOR) 2.00 (95% CI 1.48-2.71), p < 0.001]. IHD, heart failure (HF), and history of ischemic stroke were significant predictors for AKI [aOR 1.51 (95% CI 1.12-2.04), 2.87 (95% CI 2.14-3.85), and 1.47 (95% CI = 1.12-1.93), p = 0.007, < 0.001, and 0.005, respectively). Patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) were at increased risk of in-patient mortality [aOR 6.36 (95% CI 2.34-17.26), p < 0.001] and SRF [aOR 8.80 (95% CI 3.84-20.16), p < 0.001]. The presence of cardiovascular diseases and ESKD requiring RRT is a strong predictor of severe in-hospital outcomes among adult patients without chronic airway diseases who are hospitalized for hMPV infections.