Background and Purpose: The electronic referral system was established in Iran with the aim of increasing access to care, improving interaction, and efficient use of resources. The purpose of this study was to determine the effective factors in the establishment and implementation of electronic referral system in Iran. Methods: The present study was qualitative with a content analysis approach. In order to collect information, in-depth and semi-structured interviews were used. After interviewing 42 people, the information was saturated. The interviews were transcribed and analyzed, and the main topics were quoted, cited, and coded. The content analysis method was used and all authors participated in the analysis process to avoid bias and agreement. Results: Four main themes and eleven sub-themes were mentioned as effective themes in the implementation of the electronic referral system by the interviewees including resource management (human resource management, financing and equipment, and infrastructure), stewardship (policy-making, inter-sectorial leadership, and intra-sectorial governance), advocacy stakeholders (senior officials and policy-makers related to the program, service providers, community), and social commitment (commitment and accountability of service providers). Conclusions: Successful implementation of electronic referral systems requires the development of an operational plan that correctly identifies the factors affecting the establishment and implementation, as well as the cooperation of all responsible organizations which can help improve the establishment and sustainability of the program. It is suggested that managers and officials active in the field of health services use the results of this study in the establishment and implementation of electronic referral system.