OBJECTIVES: To estimate the economic impact of switching established prescription drugs (Rx) to over-the-counter drugs (OTC), for different stakeholders (patients, social insurance funds, the national economy, physicians). METHODS: An  algorithm was constructed to estimate the percentage of drugs that could be transferred from the positive and the negative list to the OTC one, based on data obtained from the OTC lists of 24 countries in Europe. In the algorithm, it was assumed that a drug could be transferred in the OTC list in Greece if it was included in the corresponding list of at least seven other European countries. Based on this approach, it was calculated that 4.3% and 40% of drugs belong to the reimbursement and negative list, respectfully, could be shifted to the OTC list. The economic impact of the switch was estimated based on the reduction of medical visits, the change of drug prices, the chance of copayments, the reduction in transportation costs and the increase of patient productivity. The analysis was stochastic. RESULTS: In the base case scenario, the total annual savings for the social funds is estimated at 170€ million and the benefit for the economy at 78,96€ million. Patients are charged with extra 95€ million for drugs. It is estimated that the switch reduces the number of medical visits by 1,8 million and saves 1,28 million days of work. An increase of individual per capital expenditure by 9.4€ due to switch to OTC drugs could benefit by 249€ million to the national economy. These results were confirmed in two additional scenarios. CONCLUSIONS: The findings of this study suggest that the Rx-to-OTC switch may reduce the health care costs of social security funds and may benefit the national economy overall, with some reasonable extra costs incurred by patients on an individual basis.