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Background: While personality predominantly influences human cognition, emotion, and behavior, there is still an unresolved research gap concerning the association between personality and substance use within the Sri Lankan context. Methods: This descriptive cross-sectional study aimed to investigate the association between personality traits and substance use among advanced-level students aged over 18 in Western province, Sri Lanka, in 2023. Data collection was carried out using selfadministered paper-pencil questionnaires. The study variables were measured using the brief version of the Big Five Personality Inventory and the Alcohol, Smoking, and Substance Involvement Questionnaire. Data analysis involved the use of the chi-square test and Spearman correlation. Findings: Of the 441 enrolled participants, 422 provided correct responses to the questionnaire. Among them, 154 (36.5%) reported substance use. The majority of students initiated substance use at the age of 17. The results reveal a significant association between the openness personality trait and substance use among advanced-level students in Western province. Additionally, there was a statistically significant positive correlation between the extroversion personality trait and amphetamine use among advanced-level students. Conclusion: The findings highlight a significant association between specific personality traits, particularly openness and extroversion, and substance use among advanced-level students in Western province, Sri Lanka. These results emphasize the significance of considering personality factors in understanding and addressing substance use behaviors among youth populations. Further research and targeted interventions are necessary to delve deeper into these associations and develop effective prevention and intervention strategies. [ABSTRACT FROM AUTHOR]