OBJECTIVES: Since 2001 in Italy several regions have introduced a fixed co-payment with some differences in the amount and exemptions. The aim of the study was to assess, through a time-series analysis, the effect of the introduction of the co-payment on pharmaceutical consumption, using, as case study, two Italian regions: Piemonte and Puglia. METHODS: Monthly data between January 2000 and December 2010 related to both public and private outpatient consumption were used in the analysis. Public consumption data were obtained from AIFA’s Medicines Utilisation Monitoring Centre (OsMeD); conversely, data on private consumption were obtained as difference between the total consumption (private and public) provided by IMS Health and public consumption. The data were expressed in Defined Daily Doses (DDD) per 1000 inhabitants. A segmented regression analysis was performed, controlling for the autocorrelation. RESULTS: In Piemonte Region the introduction of co-payment had an immediate significant effect on public consumption with a reduction of 74 DDD per 1000 inhabitants (p-value 0.007).  The private consumption showed a significant increase of 119 DDD per 1000 inhabitants (p-value0.03) after the introduction of the co-payment. In Puglia Region the co-payment didn’t have the expected outcome; in fact both public and private consumption increased after the intervention. In the long term the public consumption steadily grew and there was a significant reduction in private consumption. CONCLUSIONS: The introduction of co-payment didn’t have the expected effect in reducing the over consumption. In Piemonte Region the reduction of public consumption was balanced by the increase in private consumption (substitution effect). In Puglia Region the co-payment resulted in a lowering of private consumption, probably due to fewer available economic resources (income effect), and didn’t have any effect on public consumption.