BACKGROUND:Human parechovirus (HPeV) and enterovirus (EV) infections are widespread and can lead to a broad range of symptoms, from the common cold to severe disease (SD). Because of the lack of Italian data, this 4-year retrospective cross-sectional study aimed to investigate the frequency, seasonality and molecular characteristics of EV and HPeV circulating in children younger than 5 years. METHODS:A total of 812 samples were collected from children ≤5 years (56.5% males; median age20.6 months; interquartile range30.1 months) from September 2010 to August 2014. Two real-time RT-PCR assays were used for EV/HPeV and EV-D68 detection. Phylogenetic analysis was performed on the EV-VP1 gene and the HPeV–VP3/VP1 junction. RESULTS:16.1% and 5.2% of samples were EV- and HPeV-positive, respectively. One sample was EV-D68-positive. The majority (nearly 80%) of EV/HPeV-positive samples was detected in children ≤3 years, during the summer/autumn seasons. The risk of EV infection was higher in children presenting with SD, whereas the risk of infection from HPeV was higher in infants ≤1 year. Most (61.7%) of molecularly characterized EVs belonged to species B, followed by A (29.4%). The majority (66.7%) of characterized HPeVs were type 1, followed by types 3 (20%) and 6 (13.3%). CONCLUSIONS:This study shows the significant impact of EV/HPeV circulation in children, particularly among those ≤3 years and during and early autumn, with different pattern of viral strains. The implementation of a national surveillance system could clarify the epidemiologic and clinical characteristics of these viruses in the general population.