The marketing authorisation of a new medicine is granted on the basis of a favorable benefit-risk balance for its target population and indication.  However, not all risks will have been identified at the time when an initial authorisation is sought and many of the risks associated with the use of a medicinal product will only be discovered/fully characterised when the medicine is widely used in everyday medical practice. A full HTA should provide for an evaluation of adverse drug reactions (ADR) including those identified during long term follow- up or which are rare. In addition to knowledge of risks, a relevant consideration for both individual patients and policy makers is the performance of risk minimization measures (RMM) in everyday medical practice.  The new European pharmacovigilance legislation embeds the RMP as a key tool in proactive pharmacovigilance. The RMP, as the documented set of pharmacovigilance activities and interventions designed to identify, characterise, and prevent/minimise risks associated with exposure to a medicine, may include specific RMM. RMM should be shown to achieve the desired effect of reducing the burden of ADR and optimising health outcomes. Implementation of RMM may involve a substantial investment of resources and their performance in health care systems should be assessed. In case a RMM proves ineffective, alternative interventions must be identified implemented. We introduce an approach to evaluating the effectiveness of RMM that builds on the assessment of two distinct levels of evidence. The evaluation of the effectiveness of RMM should differentiate between the actual implementation of the RMM, and the attainment of its final objective(s). If the RMM is unsuccessful, this strategy will help to ascertain whether the intervention was inherently ineffective or badly delivered. The assessment requires research encompassing analysis of implementation (process indicators), and traditional epidemiological research addressing the attainment (final outcome indicators) of RMM.