Background: Nakhon Phanom Hospital has the main mission of serving patients in Nakhon Phanom Province, neighboring provinces, including tourists traveling across the border from Khammouane Province, Lao PDR, but due to security regulations cause delay, and there's costs more. Objective: 1) To study the problem condition of the cross-border referral system 2) To develop the cross-border referral system Methods: The purposive sampling was used by 31 persons. The instrument was a satisfaction questionnaire with accuracy (IOC) 0.67-1.00, reliability equal 0.91. the data were analyzed using frequency, percentage, mean, standard deviation, and content analysis. The study consisted of 4 steps: 1) to study the problem condition of patient referral operation 2) develop the referral system 3) test the referral system 4) evaluate the referral system. Results: 1) Important issues in the operation of the cross-border referral system were (1) the availability of care personnel during cross-border referrals; (2) the movement of personnel who refer patients across borders; (3) the emergency expressway system during the situation. COVID-19 (4) Limitations of consulting specialists in Thailand (5) Coordination according to regulations International law (6) Information system before referral via khammouane refer (7) Ambulance cannot be delivered through border country (8) Problems with national security and special circumstances (9) the needs of the patient's relatives who must be accompanied to take care of the patient; and (10) Traffic jam from Khammuan Sub-District Hospital to Nakhon Phanom Hospital. 2) The cross-border referral system consists of 3 components: 1) Human resource development by subcomponent (1) the personnel capacity development system in providing care during referral (2) the personnel governance system and transfer equipment 2) the development of the guidelines aspects by subcomponent (1) the guidelines for caring for patients with critical illnesses (2) the emergency expressway system and consulted a specialist 3) the development of information systems by subcomponent (1) the coordination according to the regulation international law (2) the information system before referral via khammouane refer, the level of satisfaction with the referral system across border found that 1) Human resource development at a high level (x ̅ = 4.49, SD. = 0.51) by subcomponent 1.1) Satisfied with the personnel capacity development system in providing care during referral at a high level. (x ̅ = 4.59, SD. = 0.49) 1.2) Satisfied with the personnel governance system and transfer equipment at a high level (x ̅ = 4.39, SD. = 0.52) 2) Satisfied with the development of the guidelines aspects at the highest level (x ̅ = 4.56, SD. = 0.50) by subcomponent 2.1) Satisfied with the guidelines for caring for patients with critical illnesses at the highest level (x ̅ = 4.55, SD. = 0.50) 2.2) Satisfied with the emergency expressway system and consulted a specialist at the highest level (x ̅ = 4.58, SD. = 0.50) 3) Satisfied with the development of information systems at the highest level (x ̅ = 4.63, SD. = 0.48) by subcomponent 3.1) Satisfied with the coordination according to the regulation international law at the highest level (x ̅ = 4.61, SD. = 0.49) 3.2) Satisfied with the patient information system before referral via khammouane refer at the highest level (x ̅ = 4.66, SD. = 0.48) Conclusion: An effective cross-border referral system requires a personnel development plan. Development of guidelines for caring for critically ill patients as well as the development of information systems to provide quality services to patients.