OBJECTIVES: From 2001 onwards, a wave of new innovative medicines has been introduced in the Greek pharmaceutical market. Based on this, the purpose of this study is to identify and quantify the effects of the increasing penetration of innovative medicines on pharmaceutical spending in Greece during the period 2001-2014, as well as the influence of patient copayments on the market shares of patented medications.  METHODS: We used data about on-patent volume, patient additional copayment, total pharmaceutical expenditure, and expenditure for on-patent medicines. Data for expenditure were approached by sales. The database was derived from the Greek National Organization for Medicines (EOF), and Greece’s main health insurance fund (EOPYY). The data were selected on the basis of the therapeutic categories that include active substances under patent protection. Our empirical investigation was based on a linear regression, an exponential form equation, and a quadratic regression. RESULTS: Our analysis suggests that pharmaceutical spending is significantly and positively associated with the volume of on-patent medicines. According to the second regression analysis, patient additional copayment is positively related to spending for on-patent medicines. The relationship between the cumulative penetration of on-patent medicines and the share of the relevant expenditure on the total pharmaceutical expenditure was found positive and statistically significant. CONCLUSIONS: According to our empirical findings, the increasing penetration of on-patent medicines during 2001-2014 contributed significantly to the pharmaceutical spending increase, while the increase of spending for on-patent medicines increases the average additional copayment. However, further research regarding the extent to which the health effects of these medicines outweigh the high cost is essential for taking evidence-based reimbursement decisions.