The high academic burden may hamper the quality of life of medical students. To evaluate the quality of life (QOL) for medical students attending a Chilean university. Four hundred eleven medical students aged 22 ± 2 years (51% women), studying in Santiago, Chile, answered online a validated Spanish version of the WHOQOL-BREF quality of life survey (scored from 0 to 100). Overall scores were assessed for the questionnaire domains Physical health, Psychological health, Interpersonal relationships, and Environment. The global scores were 65.1 for Physical health, 63.1 for Psychological health, 61.3 for Interpersonal relationships and 67.2 for Environment. Students in clinical practice, females, those with sedentary behaviors and consuming modafinil had lower Physical health scores. Students coming from outside Santiago, with sedentary behaviors and who consumed modafinil had poorer Psychological health scores. Students coming from outside Santiago, males and those with sedentary behaviors had Lower Interpersonal relationship scores. Environment scores were also lower among students who were sedentary or from outside Santiago. The variables that had a greater negative impact in the quality of life of these students were the transition from theoretical courses to clinical practice, being from outside Santiago, being overweight or obese and consuming modafinil. Students that were physically active had better quality of life scores.