OBJECTIVES: It has been argued that the selection criteria of comparator treatments suggested by the cost-effectiveness (CE) guideline in Korea are too restrictive and unrealistic for a valid CE assessment. The use of inappropriate comparators could result in an incorrect value assessment of a new drug leading to invalid reimbursement decisions. Thus, we conducted a study to investigate practical gaps in comparator selection to improve the validity of CE analysis. METHODS: We performed an online survey among all staff of the 35 member companies of the Korea Research-based Pharmaceutical Industry Association (KRPIA) whose workplace duty is related to CE evidence generation and/or submission to the government. In the questionnaire, we presented a hypothetical situation based on each of the practical gaps identified by the focus group interviews (FGI) and asked the respondents whether they had experienced it. A total of 50 out of 90 people included in the survey responded to the survey between November 11 and 26, 2014, yielding a response rate of 53.8%. RESULTS: Among the eight gaps presented in the survey, the highest proportion of respondents experienced “difficulty in obtaining reliable market share data needed to select a comparator” (94%), followed by “drug widely used for a long time selected as comparator for new drug because it was recognized as a standard treatment” (88%), “uncertainties in indirect comparison” (78%), “therapeutically nonequivalent drugs as comparators” (72%), and “price of new drug compared with price of generic product rather than initial price of original product” (70%) . The lowest number of respondents experienced “inclusion of off-label drugs as comparators” (36%). CONCLUSIONS: We expect our investigation results to improve the quality of CE guidelines for valid selection of comparators in South Korea as well as other countries, and, consequently, help assess the true value of pharmaceutical interventions.