OBJECTIVES: The therapeutic reference price (RP) system in Germany is regarded as a successful mechanism to reduce pharmaceutical spending. However, later introduced price directed measures such as the so-called payer contracts (pharmaceutical tender contracts (TC) interact with the reference price mechanism. The aim of this paper is to compare and analyse the effects of both instruments on pharmaceutical price, volume and expenditure for substances at the period around loss of exclusivity. METHODS:   A group of frequently prescribed drugs with patent expiry between the years of 2001 and 2008 are investigated and the sales and unit data in the statutory health insurance system are analysed for a period one year before and two year post patent expiry. RESULTS: The data show for the group with reference price and no tender contract (RP+/TC-) and with no reference price but tender contracts (RP-/TC+) similar level for the sales but significantly higher volume data for the first group. In the first year post patent expiry there seams to be a significant drop of sales and volume 9-12 month post patent expiry – a period, when usually the reference price is set.    The figures for the groups with tender contracts (TC+) show a more steadily decline post patent expiry. The group RP+/TC+ is in terms of cost containment (sales decline) the most prominent one.    If no regulation takes place, sales and volume increases even post patent expiry.  CONCLUSIONS: Reference pricing and tender contracts are two cost containment measures, which are equally effective if applied alone, and which have additional impact, when applied together.