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AbstractBackground In-flight medical emergencies (IMEs) are expected to increase as air travel normalized in the post-COVID-19 era. However, few studies have examined health professions students’ preparedness to respond to such emergencies. Therefore, this study aimed to investigate medical students’ knowledge, confidence, and willingness to assist during an IME in their internship program.Methods This cross-sectional survey utilized an online, self-administered questionnaire-based survey targeted at medical students at two medical colleges in Saudi Arabia. The questionnaire comprised three parts: sociodemographic characteristics, knowledge about aviation medicine (10 items), and confidence (7 items)/willingness (4 items) to assist during an IME. Odds Ratios (OR) and 95% Confidence Intervals (95%CI) were computed to detect potential associations between the knowledge levels and the other independent variables. Responses to confidence and willingness questions were scored on a 5-point Likert scale.Results Overall, 61.4% of participants had inadequate knowledge scores for providing care during an IME, and the proportion of participants did not differ between those who had or had not attended life support courses (60.4% vs. 66.7%, p > 0.99). Only frequency of air travel ≥ two times per year was associated with higher odds of adequate knowledge score [OR = 1.89 (95%CI 1.14–3.17), p = 0.02]. In addition, 93.3% of the participants had low, 6.3% had moderate, and 0.8% had high willingness scores, while 86.3% had low, 12.2% had moderate, and 1.5% had high confidence scores. There were no differences in the proportion of participants with low, moderate, and high willingness or confidence scores by attendance in life support courses.Conclusion Even though over 8 in 10 students in our study had previously attended life support courses, the overwhelming majority lacked the knowledge, confidence, and willingness to assist. Our study underscores the importance of teaching medical students about IMEs and their unique challenges before entering their 7th-year mandatory general internship.