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Renato Zambrano-Cruz,1 Gina Paula Cuartas-Montoya,1 Rosa Martha Meda-Lara,2 Andrés Palomera-Chávez,2 William Tamayo-Agudelo1,3 1Centro de Habilidades Cognitivas, Universidad Cooperativa de Colombia (Cooperative University of Colombia), Medellín, Antioquia, Colombia; 2Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara (University of Guadalajara), Guadalajara, Jalisco, México; 3Division of Psychiatry, University College London, London, UK Background: This research article addresses the relationships among personality, risk perception, and health perception. The personality construct has been one of the main topics of research in psychology throughout history and is understood as the set of traits or cognitive, affective and behavioral characteristics that an individual possesses. Important relationships have been found that show the impact of personality on people’s health as well as the impact of health conditions on the configuration of personality. This research investigates the perception of risk as a mediating trait between personality and perception of health. Materials and methods: To achieve this, a cross-sectional study was conducted in which 398 Colombians from all regions of the country were evaluated. The NEO Five Factor Inventory (NEO-FFI), The General Health Questionnaire (GHQ-12) and Health Risk Perception Test (HRPT) tests were used. Results: The data were analyzed with multiple regression and path analysis. The findings using multiple regression show that neuroticism and the personal meaning of risk affect the perception of health; however, using path analysis, model fit with the proposed model was not achieved with no mediator effect of perception of risk. Conclusion: It is necessary to focus on relationships between neuroticism and perception of health in future research. Keywords: personality, health perception, risk perception, health psychology