Introduction: Perfectionism and intolerance to frustration are the main factors of vulnerability to psychological stress observed in students of the Integrated Master Degree in Medicine of the Faculty of Medicine, University of Coimbra, a study claims. We aimed to ascertain their reasons, seeking for their prevention.Material and Methods: An observational triangulation study was performed, collecting the main reasons according to the opinion of a students focus-group, organized in a questionnaire completed with epidemiologic data, applied online to all students of the Integrated Master Degree in Medicine of the Faculty of Medicine, University of Coimbra. Statistical analysis was performed.Results: A representative sample, of n = 368, 77.7% female, was studied. The most important responded reasons were ‘intrinsic factors’ and ‘medical profession demands’, with, respectively, 91.1% and 91.8% of ’important’/’very important’ answers; ‘environmental pressure’ is the less important, with 68.2% attributing those classifications. Students satisfied with curricular life attribute less importance to ’environmental pressure’ (p = 0.004), ‘insecurity about professional training’ (p = 0.017), ‘curricular evaluation methods’ (p = 0.002) and ‘Integrated Master Degree in Medicine of the Faculty of Medicine, University of Coimbra curricular demands’ (p = 0.002); female students assign more importance to ‘Integrated Master Degree in Medicine curricular demands’ (p = 0.001); students involved in an extracurricular activity consider less important the ‘environmental pressure’ (p = 0.007).Discussion: In this Integrated Master Degree in Medicine of the Faculty of Medicine, University of Coimbra students sample, vulnerability to psychological stress associated to perfectionism and intolerance to frustration is due essentially to self-demanding personality. Insecurity about professional demands, associated to suffering in anticipation and the absence of professional perspectives, represent another important cause.Conclusion: Psychological support, involvement in specific extracurricular activities and curricular reorganisation appear to be means of reducing the vulnerability to stress in medical students.