Human metapneumovirus (HMPV) is a recently discovered cause of viral respiratory infections. We describe clinical and molecular epidemiology of HMPV cases diagnosed in children with respiratory infection at University of Malaya Medical Centre, Kuala Lumpur, Malaysia. The prevalence rate of HMPV between 2010 and 2012 was 1.1%, and HMPV contributed 6.5% of confirmed viral respiratory infections. The HMPV patients had a median age of 1.6 years, and a median hospital admission of 4 days. The most common clinical presentations were fever, rhinitis, pneumonia, vomiting/diarrhoea, and bronchiolitis. Based on the partial sequences of F fusion gene from 26 HMPV strains, 14 (54%) were subgenotype A2b, which was predominant in 2010; 11 (42%) were subgenotype B1, which was predominant in 2012; and 1 (4%) was subgenotype A2a. Knowledge of the circulating subgenotypes in Malaysia, and the displacement of predominant subgenotypes within 3 years, is useful data for future vaccine planning.