Introduction: Entrance examinations to medical school are fundamental instruments because they objectively identify applicants with the highest probability of academic success during the first year, by assessing disciplinary knowledge, cognitive skills, and critical reasoning necessary to face the complexity of biomedical sciences.  Objective: To evaluate the predictive capacity of the entrance exam, high school grade point average, and preparatory course on first-year academic performance in medical students.  Methodology:Observational retrospective cohort study with 321 students from the 2022 and 2025 cohorts. Hierarchical regression and path analysis using structural equation modeling were applied.  Results: The model explained 19.4% of the performance variance. EXANI II Ceneval (β=.242), Histology (β=.239), and high school (β=.181) showed significant direct effects. High school exerted an indirect effect through Histology (β=.041).  Conclusions: The entrance exam and the preparatory course are the most robust predictors of initial academic success in medicine.