In 2005, a Dutch health insurer introduced a financial incentive directed to general practitioners to promote rational prescribing of statins and proton pump inhibitors (PPIs). Concomitantly, a regional institution that develops pharmacotherapeutic guidelines implemented two educational interventions also aiming at promoting rational statin and PPI prescribing. Utilizing a prescription database, we estimated the effect of the interventions on drug utilization and cost of statins and PPIs over time. We measured the effect of the interventions within an implementation and a control region. The implementation region included prescriptions from the province of Groningen where the educational intervention was implemented and where the health insurer is most active. The control region comprised all other provinces covered by the database. We modelled the effect of the intervention using a state-space approach. Significant differences in prescribing and cost patterns between regions were observed for statins and PPIs. These differences however were mostly related to the concurrent interventions of Proeftuin Farmacie Groningen. We found no evidence indicating a significant effect of the rational prescribing intervention on the prescription patterns of statins and PPIs. Our estimates on the economic impact of the Proeftuin Farmacie Groningen interventions indicate that educational activities as such can achieve significant cost savings. Copyright © 2014 John Wiley & Sons, Ltd.