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Abstract Introduction Designing, developing, and implementing a course without assessing and prioritizing instructional needs may result in inefficiency due to the disregard for the actual needs of the target population. The present study aimed to determine and prioritize medical students’ instructional needs regarding Massive Open Online Courses (MOOCs) at Shiraz University of Medical Sciences. Methods This survey study was carried out in three stages (2020–2021) using the Delphi technique. Purposive and snowball sampling methods were used to select the instructors. The students were selected through simple random sampling. The first round of the Delphi technique involved a questionnaire consisting of one open-ended question, completed by 49 basic/clinical faculty members and 47 senior medical students. In the second round, a 5-point Likert scale-based questionnaire was used to prioritize the instructional needs. The reliability of the questionnaire was verified by Cronbach’s alpha coefficient. In the third round, a focus group was used. A total of six expert faculty members and one senior medical student were invited to the focus group session to prioritize the needs. Data were analyzed using Friedman’s non-parametric ranking test in SPSS version 26. Results Ten instructional needs priorities were extracted, including common pharmacotherapies (antibiotics and narcotics), prescriptions, physiology, anatomy, physical examination, electrocardiography interpretation, radiography, computed tomography scans, serum electrolyte disorders, and cardiovascular and internal (endocrine and metabolic) diseases. The chi-squared calculated value (715.584) indicated a significant difference in the importance of the questionnaire’s questions (P |