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An increase in number of motorcycles in Tanzania has resulted in higher rates of motorcycle crashes. The factors associated with the risk of motorcycle crashes include rider characteristics, riding behavior, and riding experience. This study aimed to determine the awareness and practices of commercial motorcyclists regarding motorcycle crash-related risk factors and protective measures in Mbeya, Tanzania. This cross-sectional study targeted 404 commercial motorcyclists in Mbeya, Tanzania. Data were collected using a questionnaire composed of questions on sociodemographic characteristics, and the awareness and practices of motorcyclists regarding motorcycle crash-related risk factors and protective measures. The SPSS computer software version 27 was used for data analysis. For descriptive analysis means, and proportion were used. The outcome variables were level of awareness and degree of practice. Multivariate regression analysis was utilized to analyze how participants’ sociodemographic characteristics influenced their level of awareness and degree of practice. A p-value of less than 0.05 was considered statistically significant. Overall, most (63.4%) participants had a high level of awareness regarding motorcycle crash-related risk factors and protective measures. Whereas, slightly more than half (52.2%) of participants had poor practice. Working experience of