Respiratory syncytial virus (RSV) is the leading cause of lower respiratory illness in children. Prevention of this infection is available with the use of intravenous immunoglobulin or an intramuscular humanized monoclonal antibody (palivizumab). Palivizumab has been available in Puerto Rico since 1999. The objective of this study was to follow-up infants who received RSV prophylaxis with palivizumab in Puerto Rico to assess its efficacy and safety. A total of 230 infants who received RSV prophylaxis during the 2000-2001 and 2001-2002 seasons were followed-up. Adverse events from injections were minimal including erythema (2%), fever (5%), pain (4%), and rash (2%). In none of the patients prophylaxis was discontinued due to side effects. Forty-four infants (19%) had at least one respiratory hospitalization throughout the season, with RSV confirmed in seven (3%). Most hospitalizations occurred in the month of August when infants had received only one dose of palivizumab and on December, a peak month for RSV infections. Five infants (2.2%) required admission to an intensive care unit. In none of them, RSV was confirmed. This study confirms that monthly intramuscular administration of palivizumab is effective in preventing serious RSV infections in high risk infants.