Objective: To assess influenza vaccine effectiveness against influenzalike illness (ILI) and ILI impact on health care use and school performance among college and university students. Design: Pooled analysis of 4 consecutive cohorts for the 2002-2003 through 2005-2006 seasons. Setting: Twin Cities campus of the University of Minnesota (2002-2003 through 2005-2006 seasons) and St. Olaf College in Northfield, Minnesota (2005-2006 season). Participants: Full-time students received e-mail invitations to participate in single-season cohorts. Internet-based surveys collected baseline (October) and follow-up (November-April) data. Main Exposure: Influenza vaccination. Main Outcome Measure: Proportion of students with ILI. Multivariable regression models assessed the effectiveness of vaccination for reducing ILI during months when influenza was circulating while controlling for confounders and after pooling data across the 4 cohorts. Results: There were 2804, 2783, 3534, and 3674 participants in the 2002-2003, 2003-2004, 2004-2005, and 2005-2006 cohorts respectively, and overall, 30.2% were vaccinated. In the pooled analysis, 24.1% of students experienced at least 1 ILI during influenza seasons. Vaccination was associated with a significant reduction in the likelihood of ILI during influenza seasons (adjusted odds ratio, 0.70; 95% confidence interval, 0.56-0.89) but not during noninfluenza periods (adjusted odds ratio, 0.98; 95% confidence interval, 0.73-1.30). Vaccination was also associated with significant reductions in ILI-associated provider visits, antibiotic use, impaired school performance, and numbers of days of missed class, missed work, and illness during the influenza seasons. Conclusions: Influenza vaccination was associated with substantial reductions in ILI and ILI-associated health care use and impairment of school performance. College and university students can experience substantial benefits from influenza vaccinations.