Purpose - Although the US has lagged behind international developments in health technology assessment (HTA), renewed interest in HTA in the US has been fueled by the appropriation of $1.1 billion comparative effectiveness research (CER) in 2009 and the debate over health care reform. Approach - To inform CER practices in the US, we present case studies of HTA from England/Wales and Germany: contrasting methods; relevance to the US; and impact on innovation. Findings - The National Institute of Health and Clinical Excellence (NICE) was established in 1999 to inform trusts within the National Health Service of England and Wales. It uses cost-effectiveness analysis to guide the allocation resource across preventative and curative interventions. In Germany, the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) was established in 2004 to inform reimbursement and pricing policies for the statutory sickness funds set by the Gemeinsamer Bundesausschuss (G-BA). IQWiG evaluates competing technologies within specific therapeutic areas, placing more weight on clinical evidence and the relative efficiency of competing therapies. Practical implications - Although having deep political and cultural antecedents, differences between NICE and IQWiG can be explained by perspective: the former guiding resource allocation across an entire system (macro-evaluation), the latter focusing on efficiency within the bounds of a particular therapeutic area (micro-evaluation). Given the decentralized nature of the US health care system, and the relative powers of different medical specialties, the IQWiG model presents a more suitable case study to guided CER efforts in the US.