Background: Despite an increased number of economic evaluations of tobacco control interventions, the uptake by stakeholders continues to be limited. Understanding the underlying mechanism in adopting such economic decision-support tools by stakeholders is therefore important. By applying the I-Change Model, this study aims to identify which factors determine potential uptake of an economic decision-support tool, i.e., the Return on Investment tool. Methods: Stakeholders (decision-makers, purchasers of services/pharma products, professionals/service providers, evidence generators and advocates of health promotion) were interviewed in five countries, using an I-Change based questionnaire. MANOVA's were conducted to assess differences between intenders and non-intenders regarding beliefs. A multiple regression analysis was conducted to identify the main explanatory variables of intention to use an economic decision-support tool. Findings: Ninety-three stakeholders participated. Significant differences in beliefs were found between non-intenders and intenders: risk perception, attitude, social support, and self-efficacy towards using the tool. Regression showed that demographics, pre-motivational, and motivational factors explained 69% of the variation in intention. Discussion: This study is the first to provide a theoretical framework to understand differences in beliefs between stakeholders who do or do not intend to use economic decision-support tools, and empirically corroborating the framework. This contributes to our understanding of the facilitators and barriers to the uptake of these studies.