OBJECTIVES: Numerous guidelines on conduct and reporting of health economic (HE) evaluations have been developed over several decades differing somewhat in their objectives, scope and specific recommendations. We systematically reviewed all accessible HE guidelines to identify commonalities and differences with respect to type and content of recommendations. METHODS: A systematic search of PubMed/Medline, the Centre for Reviews and Dissemination, the EQUATOR network, and websites of health technology assessment agencies and health care coverage decisionmaking bodies comprehensively identified publicly accessible HE guidelines. These were categorized as jurisdictional mandatory, jurisdictional non-mandatory or general guidelines. Data was extracted into a template devised to capture 30 fields of content. Both qualitative and quantitative analyses were performed. RESULTS: Seventy-four HE guidelines were obtained: 23 jurisdictional mandatory, 11 jurisdictional non-mandatory and 40 general. The most common topics addressed by guidelines were: sensitivity analysis (by 91%), data identification (89%), perspective (84%), choice of health outcomes (82%), assumptions (78%), valuation of resources (77%), types of costs (76%)/resources to include (74%), comparators (74%) and modeling (74%). Compared to jurisdictional guidelines, general guidelines focused on a narrower range of topics (e.g., modeling) and were less prescriptive. Although there was a level of agreement on many issues, areas of divergence were identified: study perspective (emphasis on society: 32% of guidelines; health care payer: 19%), unrelated costs in life-years gained (inclusion in base-case or sensitivity analysis recommended by 8%, exclusion by 7%), methods to value productivity losses (friction cost approach: 12%; human capital approach: 15%; other: 3%), and recommended type of sensitivity analysis (probabilistic: 28%; deterministic sufficient: 28%). CONCLUSIONS: Available guidelines for HE evaluations are diverse and cover a broad range of methodological and reporting issues. Except for specific jurisdictional needs and a few controversial issues, however, there appears to be convergence of HE guidance over time and stability of basic content.