A pentavalent rotavirus vaccine for infants became available in the United States in February 2006. By 2007, vaccination rates nationwide were estimated to be approximately 50%. We studied the effectiveness of the vaccine in a real-world setting outside of a clinical trial. All children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by enzyme-linked immunosorbent assay (ELISA [followed by genotyping if ELISA positive]) since the 1994-1995 epidemic season, presenting a unique opportunity to assess the impact of the recently introduced vaccine. The annual number of community-acquired cases over the preceding 13 years had approached or exceeded 100, with 271 cases in 2005 to 2006 and 167 cases in 2006 to 2007. In the 2007-2008 season, only 36 community-acquired cases were identified, representing an 87% reduction from the same period in 2005 to 2006. G3 was the predominant serotype, accounting for 15 community cases (42%). Our study is limited by its observational design using historical comparisons. Nonetheless, the abrupt decline in rotavirus gastroenteritis cases during the 2007-2008 season likely resulted from vaccination. Because protection rates appeared to have exceeded vaccination rates, herd immunity may have contributed to some degree to the effectiveness of the vaccine.