BackgroundWhile the non-communicable disease (NCD) burden in the countries of the Gulf Cooperation Council (GCC) (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates) has surged over the past decades, the costs and return on investment (ROI) of implementing cost-effective, WHO-recommended NCD interventions have not been established.MethodsWe performed an economic analysis to estimate the ROI from scaling up four sets of NCD interventions over 15 years. We estimated the direct costs of the four main NCDs (cancer, diabetes, cardiovascular diseases and chronic respiratory diseases) using a prevalence-based, bottom-up cost-of-illness approach. We estimated indirect costs based on productivity loss due to absenteeism, presenteeism and premature deaths. We costed the scaling up of interventions using the WHO Costing Tool and assessed the health impact of interventions using the OneHealth Tool. We calculated ROI by comparing productivity and social benefits with the total costs of implementing the interventions.ResultsThe four main NCDs cost the GCC economy nearly US$50 billion in 2019, equal to 3.3% of its gross domestic product. The indirect costs are estimated at US$20 billion or 40% of the total burden. Implementing the four modelled intervention packages in the six GCC countries over 15 years will cost US$14 billion, with an ROI of US$4.9 for every US$1 invested and significant health and social benefits, including 290 000 averted premature deaths.ConclusionBased on the results of these six investment cases, we recommend actions to scale up current WHO-recommended cost-effective interventions, strengthen whole-of-government action, drive the NCD legislative agenda, build out the evidence base, generate additional advocacy material, and increase regional collaboration and data-sharing to establish best practices and monitor impact.