Cost Effectiveness Analyses (CEA, including cost-effectiveness and cost-utility evaluations) need to respect international methodological guidelines to provide reliable information in different countries. Cost-effectiveness is a relative concept so if the comparator is inappropriate, then the results will be unsuitable for decision-making purposes. Therefore, one of the most important structural choices of a CEA is the comparator choice. OBJECTIVES: The objective of this study was to identify a standard way to define the most appropriate comparators in a CEA according to international guidelines. METHODS: We analyzed 29 country-specific economic evaluation guidelines available online, in Chinese, Dutch, English, Portuguese and Spanish, on the ISPOR website section, “Pharmacoeconomic Guidelines around the World” in June 2016. The parts related to the comparator choice were identified by the words “comparator”, “compare”, “alternatives”, and “intervention”. The most frequently advised ways to define the appropriate comparators were identified. RESULTS: In the 29 countries, the most commonly used comparator was the "standard of care for local practice" (86%). The “watchful waiting or doing nothing” possibility was advised to consider in 45% (N=13) of the guidelines. The “therapy that prescribers would most replace with the proposed drug” was cited to be a good comparator in 38% (N=11) of the guidelines. The "lowest cost alternative" was a comparator of choice in 24% (N=7) of the guidelines. “Unauthorized drug” (i.e. no marketing authorization) used in clinical practice was to consider according to 21% (N=6) of the guidelines. CONCLUSIONS: Even if the most commonly advised comparator was the "standard of care for local practice", heterogeneity in the definition of a relevant comparator to consider for a CEA was identified among countries. Further analyses of the assessments made by Health Technology Assessment agencies would help to precise the most appropriate comparators for Cost Effectiveness Analyses.