In recent years, motorcycle ownership has significantly increased, particularly in urban areas. Although in developed economies the use of this mode of transport is not so popular, in developing countries it is one of the most widespread modes. Powered two three-wheelers (PTWs) were responsible for 21% of worldwide road fatalities for 2021, while in many countries the decrease in total road fatalities for motorcycles for the last decade is considerably lower compared to passenger vehicles. The main factors that contribute to motorcyclist incidents and crashes can be grouped in the following three main categories: human factors, road-environment factors and vehicle factors. The main objectives of this study are to review, identify and compare the main factors of PTW crashes and fatalities on a global scale. An in-depth literature review was carried out to identify and classify the main factors that contribute to PTW incidents, crashes and fatalities. Both developed and developing countries were examined. Statistical analyses were performed utilizing worldwide data to compare and identify the patterns that are related to high rates of PTW fatalities. Socioeconomic data, as well as legal regulations and driving behaviour patterns, were examined for the study. Finally, major policy implications are suggested based on the research findings to improve motorcycle safety. The identification of the critical aspects of motorcyclist crashes can efficiently contribute to the prevention and reduction of motorcycle-related fatalities and injuries.