Since the initial discovery of RSV-A ON1 in Canada in 2010, ON1 has been reported worldwide, yet information regarding its clinical impact and severity has been controversial. To investigate the clinical relevance of RSV-A ON1,acute respiratory infection (ARI) cases enrolled to our population-based prospective pediatric ARI surveillance at Khanh Hoa General Hospital, Central Vietnam from January 2010 through December 2012 were studied. Clinical-epidemiological information and nasopharyngeal samples were collected. Multiplex PCR assays were performed for screening 13 respiratory viruses. RSV-positive samples were further tested for subgroups (A/B) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region. Statistical analysis was performed to evaluate the clinical-epidemiological characteristics of RSV-A ON1. A total of 1854 ARI cases were enrolled and 426 (23.0%) of them were RSV-positive. During the study period, RSV-A and B had been co-circulating. NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012. RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1. Moreover, multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 (95% CI: 1.37-3.72) times, and radiologically-confirmed pneumonia was 1.98 (95% CI: 1.01-3.87) times greater in ON1 compared to NA1 cases. Our result suggested that ON1 ARI cases were clinically more severe than NA1.