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Introduction: Road traffic crashes (RTCs) are a leading cause of death and disabilities and impose a significant burden on the healthcare system and economy of Saudi Arabia. Around 20% of all hospital beds are occupied by victims of RTCs, which represent approximately 80% of trauma deaths occurring in these facilities. Using a seatbelt is an effective method to reduce traffic deaths and minimize the extent of associated injuries. However, little is currently known about the prevalence and predictors of seatbelt use in Saudi Arabia. More studies are needed to determine the trends of seatbelt use and study the relationship between individual factors and compliance with seatbelt use laws. The aim of the present study is to examine the prevalence and predictors of seatbelt use using the National Saudi Biobank dataset.Materials and Methods: This cross-sectional study was conducted using an in-person survey from the Saudi National Biobank (SNB). The participants were adults affiliated with the Ministry of National Guard Health Affairs in Riyadh who were examined between 2017 and 2019. Chi-squared and Wald tests were used to assess the association between the respondents' characteristics and their seatbelt use. In addition, logistic regression models were constructed to assess the univariate and multivariate associations between seatbelt use and potential predictors. All statistical tests were two-sided, and the findings were considered significant at P < 0.05.Results: A total of 5,790 adults participated in the survey. The majority of the participants (52.44%) were between 18 and 25 years old, half were males, and 58.80% were single. About 42.83% of the participants reported consistent seatbelt use as drivers or passengers. In the multivariable analysis, females were 86% less likely to wear seatbelts than males (OR = 0.136, 95%CI = 0.107–0.173). Individuals who rated their mental health as “weak” were 26% less likely to wear seatbelts than those who reported “excellent” mental health status.Conclusion: Seatbelt use remains low in the country and substantially lower than in developed countries. Young adults, females, and individuals reporting suboptimal mental health were less likely to fasten their seatbelts. These findings are valuable for public health programs to target specific groups and raise awareness about the need to increase seatbelt compliance and reduce traffic injuries.