Antiretroviral therapy (ART) has been able to transform HIV infection into a chronic disease. However, ART adherence remains an important barrier and personality traits have been postulated as a factor to be considered. This study aims to identify personality traits that can affect ART adherence, taking into account other potentially influencing factors. Case-control study. Controls and cases were classified using the percentage ART dispensation as recorded in the Hospital Pharmacy database. Controls were defined as people living with HIV/AIDS (PLWHA) with percentage ART dispensation during the last year >95% and cases were defined as PLWHA with percentage ART dispensation during the last year <90%. Sociodemographic, clinical parameters of HIV infection, psychopathological and neuropsychological factors were collected. Personality was assessed using the NEO PI-R Personality Inventory, questionnaire based on the Five Factor Model of Personality. Statistical analysis was performed using logistic regression (SPSS v.22). 125 PLWHA were included: 79 controls and 46 cases. After adjusting for confounding variables, logistic regression analysis showed that poor adherence was associated with Neuroticism (OR 1.2, 95%CI: 1.021-1.385) and Impulsivity (N5) (OR 1.5, 95%CI: 1.066-2.163). In contrast, each additional point in Order (C2) (OR 0.8, 95%CI: 0.679-0.992) or Values (O6) (OR 0.8, 95%CI: 0.710-0.974) were associated with good ART adherence. Personality is a variable to be considered in ART adherence. Implementation of the personality in the assessment of PLWHA helps identify those individuals potentially more likely to exhibit poorer ART adherence.