Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live, attenuated S(79) mumps virus vaccine has been licensed for pediatric use since 1990. There has been no assessment of its efficacy. Thus, the objective of this study was to determine the effectiveness of live, attenuated S(79) mumps virus vaccine against clinical mumps. Cases were selected from the China Information System for Disease Control and Prevention during September 2004 to March 2005. Each case was matched to a control by gender, age, and area of residency. In all, 469 cases and 469 controls were enrolled in the study. Vaccination information was obtained from the Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for one or two doses of S(79) vaccine, with 95% confidence intervals (CI). VE of mumps virus vaccine for one dose versus none was protection of 86.0% (95% CI, 77.2% to 91.5%) of recipients, and VE was much higher in the first 4 years than in the 5 to 12 years after vaccination. The S(79) vaccine can effectively prevent clinical mumps, and a second dose of mumps virus vaccine is necessary for the protection of children in China.