Professional driving is a very demanding task. According to the recent scientific evidence, Bus drivers tend to report high levels of occupational stress, burnout and occupational traffic accidents. With the implementation of new transportation modes, some substantial benefits and adverse circumstances for public transport operators have been documented. BRT (Bus Rapid Transit) systems have been implemented in different cities worldwide as an efficient alternative to fulfill difficulties and limitations related to traditional Urban Bus systems. However, in order to compare the efficiency of different public transport modes, it is important to assess, in addition to objective indicators, the incidence of psychosocial factors and other work-related issues over its operators. Aim: The aim of this study was to compare job stress, burnout, health indicators and traffic accidents suffered between two samples of professional bus drivers: Urban/City Bus and BRT (Bus Rapid Transit) drivers. Methods: The study sample was composed by 361 Colombian male Bus drivers with a meanage of 41.46 years, 222 of them working in Urban Bus companies, and 139 in BRT companies. It was designed a questionnaire composed by four sections: a) demographics and accident rates, b) job stress, c) burnout, and d) health indicators. Results: Significant differences were found between urban and BRT drivers for the case of different work-related variables, i.e., occupational stress, burnout and traffic accident rates, being these results more adverse, in all cases, for Urban Bus operators. Furthermore, both BRT and urban bus drivers reported elevated prevalence of adverse health habits and results. Conclusions: This study showed that the prevalence of work-related stress and burnout are significantly elevated among Colombian bus drivers. In addition, it was found that the bus drivers’ job stress is related to burnout indicators. Comparatively, BRT drivers tend to present better outcomes in terms of occupational stress, burnout and occupational accidents than Urban Bus operators. The intervention on these factors represent a potentially successful alternative for the prevention of occupational traffic accidents and negative health outcomes in Bus drivers.