BACKGROUND Mexico implemented routine childhood vaccination against rotavirus in 2007. We describe trends in hospitalization and deaths from diarrhea among children aged <5 years in Mexico before and 7 years after implementation of rotavirus vaccination. METHODS We obtained data on deaths and hospitalizations from diarrhea, from January 2003 through December 2014, in Mexican children <5 years of age. We compared diarrhea-related mortality and hospitalizations in the postvaccine era with the prevaccine baseline from 2003 to 2006. RESULTS Compared with the prevaccine baseline, we observed a 53% reduction (95% confidence interval [CI], 47%-58%) in diarrhea-related mortality and a 47% reduction (95% CI, 45%-48%) in diarrhea-related hospitalizations in postvaccine years, translating to 959 deaths and 5831 hospitalizations averted every year in Mexican children aged <5 years. Prevaccine peaks in diarrhea-related mortality and hospitalizations during the rotavirus season months were considerably diminished in postvaccine years, with greater declines observed during the rotavirus season compared with non-rotavirus season months. CONCLUSIONS We document a substantial and sustained decline in diarrhea-related hospitalizations and deaths in Mexican children associated with implementation of rotavirus vaccination. These results highlight the public health benefits that could result in countries that adopt rotavirus vaccination into their national immunization programs.