OBJECTIVES: Comparative effectiveness research (CER) methods guides have recently been released by two main CER funding agencies, the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI). We evaluated and compared these methods guides to identify consensus in recommended CER methodologies. METHODS: CER methods recommendations from each document were assessed and areas of overlap were identified. RESULTS: The PCORI Methodology Report (November 2013) made 40 CER methods recommendations. The AHRQ User Guide (January 2013) made 57 CER methods recommendations. These methods recommendations related to the following 10 methods topics: study protocol and design, patient-centeredness, heterogeneity of treatment effect (HTE), causal inference, diagnostic tests, systematic reviews, comparator selection, study variables, data concerns, and statistical analysis. Of the 57 specific recommendations made in the AHRQ guide, 24 (42%) were also made in the PCORI guide. For example, both documents support identifying gaps in evidence, explaining specific impacts of the research, developing a formal study protocol, and assessing the adequacy of data sources. Furthermore, these documents both support rigorous measurement and analysis of confounders, precisely defining exposures and outcomes, and pre-specification of data analysis plans. Both documents also supported the selection of appropriate comparators and identifying and assessing participant subgroups. Non-overlapping recommendations mostly addressed more specific methodology topics and issues including missing data, data registries, data networks, and patient-centeredness. These unique recommendations highlight areas for further debate and discussion regarding best practices in CER methods.  CONCLUSIONS: Based upon our synthesis of CER methods recommendations, agreement was high between the AHRQ and PCORI guides. We identified a list of core CER recommendations based on the overlap of these two methods guides which may aid researchers in the conduct of CER.