This study investigates safety challenges in transportation in Nigeria across the six geopolitical zones of the country comprising South-South, South-East, North-West, North-Central, North-East and South-West geopolitical Zones. Both primary and secondary data were employed, and the Multinomial Logistic Regression Model, with specific adoption of the Relative Risk Ratio approach, is the method of analysis. The main concern is examination of exposed and unexposed commuters in the various locations to determine the degrees of exposure to risks associated with ‘basket’ of modes, state of infrastructures and specific risk factors, which account for the fatalities observed on the different roads under consideration. It is found that the six geopolitical zones have various degrees of risks exposure while North-West, North-Central and South-West zones showed significant risk difference between the exposed and the unexposed groups due to risk factors such as bad roads, road blockage/obstruction, kidnaping, unmaintained vehicles, overloading, over speeding and other forms of reckless use of the roads etc. The study recommends risk avoidance education to commuters as new strategies in vulnerable zones and increased deployment of well-trained community road marshals and other relevant security personnel to monitor situations and provide safety for road users. Also, a working transportation policy must be evolve to mitigate the risk factors highlighted above.