OBJECTIVES:    In Europe, Health Technology Assessment (HTA) bodies produce coverage decisions that guide public funding of pharmaceuticals.  This analysis examines and weights those factors that drive HTA coverage decisions, focusing on the National Institute for Health and Clinical Excellence (NICE) in England and Wales, the Scottish Medicines Consortium (SMC), the Dutch College voor Zorgverzekeringen (CVZ), and the French Haute Autorité de Sante (HAS).  METHODS:   A dataset of approximately 1000 HTA coverage decisions by NICE, SMC, CVZ and HAS from the period 2004-2009 was created, containing more than 30 clinical, economic, process and socio-economic factors extracted from published HTA reports.  A three-category outcome variable was used, defined as the decision to ‘recommend’, ‘restrict’ or ‘not recommend’ a technology.  Multivariate analyses were conducted to assess the relative contribution of the explanatory variables on coverage decisions both within and between HTA bodies.  RESULTS:   Different combinations of clinical/economic evidence, process and socio-economic factors drive HTA coverage decisions by NICE, SMC, CVZ and HAS.  In addition, the same factor may behave differently according to the nature of the coverage decision.  The analysis further suggests there is a significant difference between HTA bodies in the probability of reaching a ‘restrict’ or ‘not recommend’ decision outcome relative to a ‘recommend’ outcome, adjusted for evidence, process and context factors.   CONCLUSIONS:   This analysis contributes to the understanding of factors driving HTA coverage decisions by examining multiple European HTA bodies, enhancing the comprehensiveness of the factors examined through descriptive and multivariate analyses and by identifying and weighting the key drivers of the coverage decisions made by the four HTA bodies between 2004 and 2009.  This research further provides relevant insights to variation among HTA bodies in the determination of patient access to pharmaceuticals, and implications for collaboration between European HTA bodies.