Professional success depends on more than just academic achievements frequently defined and evaluated as grades, academic averages and approval of semesters. Other non-cognitive factors, such as 'grit', or academic persistence, have been related to a decrease in academic dropout and success prediction. But it has not been measured in medical students. This study seeks cross-cultural psychometric validation in Spanish of the GRIT-S questionnaire in its original version to measure academic persistence in medical students. Cross-cultural adaptation of the questionnaire was carried out based on the ISPOR standards (cultural translation and adaptation of texts). The final questionnaire was applied to 427 medical students. Confirmatory factor analysis was performed. The analysis was performed with Lisrel 9.30 student version. The questionnaire did not show difficulty in content or comprehension on the part of the students. The exploratory factor analysis identified two constructs: Consistency in interests and persistence of effort. A confirmatory factor analysis was performed with a sample size of 427 subjects. The overall fit indices indicate good fit: Root Mean Square Error of Approximation (RMSEA) 0.0509 (< = 0.08), Normed Fit Index (NFI) 0.978 (> 0.9), Comparative Fit Index (CFI) 0.996 (> 0.9), Standardized RMR (SRMR) 0.0361 (< 0.08), chi-square p-value 0.217. The GRIT-S questionnaire in Spanish is a feasible, valid, and change-sensitive tool when applied to medical students. It presents psychometric properties comparable to the original questionnaire, allowing its application for future studies and interventions focused on the academic success of this population.