Background The exposure of students to stressful events and the association of these events with students’ mental health is an important matter in Medical Education. To address this arduous training and solve emerging problems, some students develop methods to help them and, among these, resilience. A hybrid learning system, merging active and traditional learning, can be a supplementary source of stress generation , since it demands the acquisition of knowledge by the students, for summative assessments of traditional teaching as well as for the autonomous search for knowledge, skills, and attitudes required in the problematization. Purpose To determine the degree of resilience throughout the medical course under the hybrid teaching-learning system, identifying underlying mechanisms. Methods This was a cross-sectional study developed from August 2017 to August 2018, at Christus University Center, Brazil, a medical school that uses problem-based learning curricula associated with traditional teaching methodology. Wagnild and Young Resilience Scale was applied to medical students from all semesters. Socioeconomic, emotional and self-reported performance variables were also collected. The association between variables was assessed with minimally adjusted logistic regression models. Results 173 medical students participated in this study, with a mean age of 22.4 years, of which 65.3% were females. 88.1% of the medical students showed high or very high resilience. Receiving support from family and friends was associated with better resilience (p values lower than 0.001), as students who were “very satisfied” or “satisfied” with family support had a greater tendency to develop better degrees of resilience, with results of “very high resilience trends” (82.50%) and “high resilience trends” (71.10%) surpassing the prevalence identified in dissatisfied students. Also, having a religious belief was also associated with higher resilience degrees (p value = 0.02). Conclusions Factors identified in this study, mainly the importance of the support network from family and friends can be stimulated in order to improve students’ resilience. There was no direct association between the academic performance self-assessment and the students’ resilience and the resilience of medical students tends to remain constant throughout the course.