Objectives Economic evaluation has increased due to the emergence of national health technology assessment (HTA) agencies. This study aims to develop a country-specific guideline for conducting economic evaluation in the Kingdom of Saudi Arabia (KSA) as an HTA component to determine the value for money of new health interventions. Methods The study conducted a real-time Delphi survey using 17 items from the method component of the Consolidated Health Economic Evaluation Reporting Standards checklist as foundation for guidelines. Consensus was reached for the relevance of guideline recommendations for the KSA healthcare system. We set a threshold of 80% for agreement and an interquartile range less than three on a nine-point Likert scale. Interim analysis provided feedback for recommendations of items if no consensus exists. A natural language processing (NLP) approach was employed to examine the relationship between experts’ comments and consensus decisions. Results The study recruited 78% experts with an average response progress rate of 97.2%. Interim analysis provided a 63% adjustment rate for recommendations with the majority requiring further clarification (65%). The guidelines concluded with a consensus on 76% of recommendations, while four remained undetermined, namely, choice of discount rate, use of same rates for health benefits and costs, outcome selection, and gross costing. The NLP results supported the consensus decision. Conclusions Expert consensus contributed to the development of informative guidelines relevant to KSA. The guidelines serve as a reference case, thus providing a foundation for HTA practices, reimbursement decisions, and future research for the KSA and its neighboring countries.