Monitoring self-medication practice, which refers to individuals using medicine without instructions of physicians, is critical to control its harmful effects. However, in Vietnam, evidence about self-medication among individuals in highland areas is constrained. This study examined self-medication practice among residents living in highland areas in Vietnam and determined associated factors. A cross-sectional study was performed in five highland provinces with 1000 individuals. Information about individual and household's socioeconomic status and self-medication practice in the last 12 months was surveyed. Multivariate logistic and Poisson regressions were used to identify associated factors with self-medication. 83.3% reported self-medication in the last 12 months, with the mean times of self-medication being 4.5 times (SD=4.1). Female (OR=0.62, <0.01), ethnic minorities, higher number of members having health insurance in family (OR=0.82, <0.01) and higher annual household income (OR=0.78, <0.05) were associated with the lower likelihood of "Only buy medicines at pharmacy stores when having illness in the last 12 month". Moreover, people who were females (OR=0.59, <0.05), white-collar worker (OR=0.25, <0.01) and had higher number of children in the family (OR=0.68, <0.05) were less likely to practice self-medication. People who were ethnic minorities, white-collar worker (Coef.=-0.32, <0.01) and higher number of members having health insurance in family had lower times of self-medication in the last 12 months compared to other groups. Meanwhile, individuals having higher number of members in the family (Coef.=0.07, <0.01) and higher annual household income (Coef.=0.08, <0.01) had highertimes of self-medication in the last 12 months. Residents in highland areas in Vietnam had a considerably high 12-month prevalence of self-medication. Medical products quality management and self-medication guideline are potential to maximize the effects of self-medication. Moreover, promoting the use of health insurance should also be concerned as a solution to address this issue.