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Ex-premature infants are more predisposed to complicated primary respiratory syncytial virus (RSV) infection. The aim of the present study was to validate the risk factors found in a previous epidemiologic case-control study regarding hospitalization as a result of RSV infection in premature infants born at 32–35 weeks of gestational age (WGA) in Spain.A prospective 2-cohort study was conducted during the 2005–2006 (October 2005 to April 2006) and 2006–2007 (October 2006 to April 2007) RSV seasons, respectively. Cases were premature infants hospitalized for RSV infection whereas controls were premature infants of the same age who did not require any hospitalization for respiratory causes.During the study period 5441 children from 37 Spanish hospitals were included in the risk factor analysis. Two hundred two (3.7%) were cases and the rest controls. Of the cases, 17.8% were admitted to the intensive care unit and 7.4% required mechanical ventilation. None of the patients died. Logistic regression analysis demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants (32–35 WGA) was associated with the following factors: absolute chronologic age of ≤10 weeks at the onset of RSV season [odds ratio (OR): 2.99; 95% confidence interval (CI): 2.23–4.01]; presence of school-age siblings or day care attendance (OR: 2.04; 95% CI: 1.53–2.74); and smoking during pregnancy (OR: 1.61; 95% CI: 1.16–2.25).In premature infants (32–35 WGA), only 3 independent risk factors were found to significantly increase the risk of RSV-related respiratory infection and hospitalization.