BACKGROUND: We observed an increase in the number of rotavirus cases in the St. Louis area during the 2012-2013 rotavirus season compared with recent seasons. We aimed to determine whether the rotavirus cases during the 2012-2013 rotavirus season were of types not included in licensed vaccines. METHODS: Microbiology laboratories of 3 children's hospitals in St. Louis provided samples that were positive using rapid antigen tests from 2010 to 2013. The majority of samples were from St. Louis Children's Hospital. We determined rotavirus genotypes by polymerase chain reaction tests and further characterized a subset of viruses by genome sequencing and comparative sequence analysis. RESULTS: Eighty-six percent (24 of 28) of typed viruses analyzed from the 2012-2013 rotavirus season were G12. We performed whole genome sequencing on 8 G12 viruses, all of which were VP4 type P. The sequenced viruses showed differences from vaccine strains in major antigenic epitopes on the VP7 protein, but most epitopes on VP4 were conserved. Rotavirus vaccine histories were available for 11 G12 cases, of whom 10 had not been vaccinated. CONCLUSIONS: G12 was a dominant community-wide genotype in 2013. Most of the G12 cases for whom vaccine histories were available had not received rotavirus vaccine. The experience demonstrates the potential for rapid shifts in rotavirus genotype distribution and underscores the need for vigilant surveillance to detect unusual genotypes that might escape from vaccine protection.