Mumps outbreaks among fully vaccinated young adults have raised questions about potential waning of immunity over time and need for a third dose of the measles, mumps, rubella (MMR) vaccine. However, there are currently limited data on real-life effectiveness of the third-dose MMR vaccine in preventing mumps. Here, we used a deterministic compartmental model to infer the effectiveness of the third-dose MMR vaccine in preventing mumps cases by analyzing the mumps outbreak that occurred at the University of Iowa between August 24, 2015, and May 13, 2016. The modeling approach further allowed us to evaluate the population-level impact of vaccination by different timing in relation to the start of the outbreak and varied coverage levels, and to account for potential sources of bias in estimating vaccine effectiveness. We found large uncertainty in vaccine effectiveness estimates; however, our models showed that early introduction of a third dose of MMR vaccine during a mumps outbreak can be effective in preventing transmission. School holidays, such as the winter break, likely played important roles in preventing mumps transmission.