Objective: Work settings with high levels of stress are consistently associated with poor health outcomes. This study examines the longitudinal relationships between the number of hours of driving a bus in a city and blood pressure and musculoskeletal problems. Methods: A prospective longitudinal design coupled with multilevel random coefficient modeling was used to examine the relationship among exposure to a job with high level of stress, urban bus driving, blood pressure, and musculoskeletal problems. Baseline blood pressure and musculoskeletal symptoms of men and women (n = 88) were assessed before they began driving a bus in central Stockholm. The number of hours of driving per week, blood pressure, and musculoskeletal symptoms were tracked for a period of 5 years. Multilevel random coefficient modeling techniques were used to model how individual trajectories of health effects were affected by the number of hours of driving, after statistically controlling for baseline preworking health measures. Results: Controlling for sex and baseline health outcomes, the average number of hours of bus driving per week predicted higher diastolic blood pressure (B = 0.069, standard error = 0.034, p =.042) and more frequent musculoskeletal symptoms (B = 0.013, standard error = 0.003, p < .001). Conclusions: The findings provide evidence for a positive association between the number of hours of bus driving and blood pressure and musculoskeletal problems. These findings are discussed in exposures to potentially toxic physical and psychosocial work-related factors.