OBJECTIVES: The recently made coverage decisions by the UK's NICE, Scotland's SMC and the allocation of $1.1 billion for comparative effectiveness research by the U.S. are strong indicators of trends in pricing and reimbursement that are likely to be observed in the future. To gain an additional insight into these trends, we analyzed the cost effectiveness studies for the top twenty highest selling drugs (~$90-100B worldwide sales). METHODS: The Top 20 drugs were selected based on their worldwide sales. For this analysis, we segmented these drugs into categories such as primary care, specialty, small molecules, biologics, therapy areas, and availability of generic alternatives. We analyzed the cost effectiveness studies that were published in peer-reviewed journals. Searches were  conducted using generic names of the drugs and the phrase "cost effectiveness" in an abstract of the published study. RESULTS: Between 2007-2012, the number of published studies on "cost effectiveness" has increased by more than 32%. There is a large variability in CERs for same drugs for different indications, in some cases also varying by biomarkers. Primary care drugs had lower and less variable CERs than specialty drugs. Variations also exist in methodology used by different groups in modeling cost effectiveness, especially for time horizon and comparator. The majority of primary care drugs were modeled for a time horizon of 35-40 years or for a lifetime to demonstrate cost effectiveness. CONCLUSIONS: This analysis shows the range, variability, and methods used for calculation of ICER values for these high budget impact drugs and provides lessons for executives and policy makers.