To analyze the epidemiology of a nationwide mumps epidemic in the Netherlands, we reviewed 1,557 notified mumps cases in persons who had disease onset during September 1, 2009–August 31, 2012. Seasonality peaked in spring and autumn. Most case-patients were males (59%), 18–25 years of age (67.9%), and vaccinated twice with measles-mumps-rubella vaccine (67.7%). Nearly half (46.6%) of cases occurred in university students or in persons with student contacts. Receipt of 2 doses of vaccine reduced the risk for orchitis, the most frequently reported complication (vaccine effectiveness [VE] 74%, 95% CI 57%–85%); complications overall (VE 76%, 95% CI 61%–86%); and hospitalization (VE 82%, 95% CI 53%–93%). Over time, the age distribution of case-patients changed, and proportionally more cases were reported from nonuniversity cities (p<0.001). Changes in age and geographic distribution over time may reflect increased immunity among students resulting from intense exposure to circulating mumps virus.