Objective: To determine if a clinic system to assess and vaccinate preschool-age children at every clinic visit can improve vaccination rates., Design: A nonequivalent control group design contrasting an intervention clinic with a comparison clinic., Setting: Two urban St Paul, Minn, clinics. The intervention clinic is a family practice residency clinic, and the comparison, clinic is a community health center clinic., Patients: Primarily a low socioeconomic status white population., Interventions: A clinic-wide system to identify and vaccinate children at all clinic visits. Appointment personnel, medical assistants, and physicians all had roles in the intervention protocol., Main Outcome Measures: Percentage of children at the 2 clinics who were up-to-date for a primary vaccine series at age 24 months and also at the end of the study collection periods, preintervention and postintervention., Results: The intervention clinic improved the percentage of children up-to-date for a primary vaccine series at age 24 months from 42% to 56% (P = .02), while the percentage at the comparison clinic did not change significantly (P = .81). Similarly, the intervention clinic improved the percentage of children up-to-date for age at the end of the study periods from 49% preintervention to 63% postintervention (P = .02), while the percentage at the comparison clinic did not improve significantly (P = .45). The system was especially useful for children with few visits to the intervention clinic., Conclusions: Although the intervention clinic resulted in a substantial improvement in vaccination rates for preschool-age children, rates remained well below national goals. A combination of clinic, community, and national initiatives may be needed to ensure appropriate vaccination rates for this challenging patient population.