In the current research the Sunflower methodology is implemented and evaluated for the assessment of the road safety level of the powered two-wheelers in Greece, a road users group with increased road accident risk in Greece and worldwide. The Sunflower methodology is based on a holistic approach of all road safety components under the form of a pyramid, which consists of five distinct levels: structure and culture, road safety measures and programmes, safety performance indicators, number of casualties (fatalities and injuries) and accidents and finally the road accident social costs. For the implementation of the Sunflower methodology on the powered two-wheelers road safety in Greece, data and information at all levels of the pyramid were analysed and exploited, while availability of all necessary data/information was identified and assessed. The implementation of the Sunflower methodology revealed that the increased accident risk of the powered two-wheelers in Greece can be mainly attributed to the high number of motorcycles and mopeds, as well as to the inappropriate behaviour of the powered two-wheeler riders towards active and passive safety.  Moreover, the gradual and conditional incorporation of the powered two-wheel vehicles in the Greek traffic system, emphasizing on the improvement of the driving behaviour of the drivers of all vehicle categories, could be considered as the basic recommendations for the reduction of accident risk and severity of powered two-wheelers in Greece.