To evaluate the effect of palivizumab prophylaxis on hospitalization for acute respiratory tract infections (RTI) in preterm infants, a prospective study was performed on a cohort of preterm infants [gestational age (GA) <32 weeks], admitted at birth to a Neonatology Intensive Care Unit (NICU) (follow-up: 30-month after discharge). 154 palivizumab-recipients and 71 palivizumab-non-recipients were evaluated. During follow-up, a similar rate of hospitalization for RTI was found in the two groups (11.3% in palivizumab-non-recipients and 15.58% in palivizumab-recipients, p=0.39). However, when only infants hospitalized during their first respiratory syncytial virus (RSV) epidemic season and with a chronological age <6 months at admission were considered, the incidence rates for hospitalization was six-fold lower in the palivizumab-recipients (p=0.007). This study contributes to the definition of epidemiological data on RTI among preterm infants in Italy. These data support the usefulness of palivizumab prophylaxis for prevention of hospitalization for RTI in young preterm infants during the expected RSV epidemic season.