OBJECTIVES: To increase adult immunizations at inner-city health centers serving primarily minority patients. DESIGN: A before-after trial with a concurrent control. SETTING: Five inner-city health centers. PARTICIPANTS: All adult patients at the health centers eligible for influenza and pneumococcal vaccines. INTERVENTION: Four intervention sites chose from a menu of culturally appropriate interventions based on the unique features of their respective health centers. MEASUREMENTS: Immunization and demographic data from medical records of a random sample of 568 patients aged 50 and older who had been patients at their health centers since 2000. RESULTS: The preintervention influenza vaccination rate of 27.1% increased to 48.9% (P<.001) in intervention sites in Year 4, whereas the concurrent control rate remained low (19.7%). The pneumococcal polysaccharide vaccine (PPV) rate in subjects aged 65 and older increased from 48.3% to 81.3% (P<.001) in intervention sites in Year 4. Increase in PPV in the concurrent control was not significant. In logistic regression analysis, the likelihood of influenza vaccination was significantly associated with the intervention (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.77-2.41) and with age of 65 and older (OR=2.0, 95% CI=1.62-2.48) but not with race. Likelihood of receiving the pneumococcal vaccination was also associated with older age and, to a lesser degree, with intervention. CONCLUSION: Culturally appropriate, evidence-based interventions selected by intervention sites resulted in increased adult vaccinations in disadvantaged, racially diverse, inner-city populations over 2 to 4 years.