This study proposes a framework for developing a pro-active system aiming at reducing motorway crash risk based on risk indicators. Although motorways are of safe road type by design, a crash if happens would be really severe. Reducing motorway crash risk would prevent crashes or diminish their severity. To that purpose, risk indicators are tested and validated with real data including traffic data, meteorological data, and crash databases from a study site in Switzerland. A guideline about how to define the risk criteria is proposed and applied in a simulation model which is the platform for implementing a pro-active crash risk prevention system. The model is calibrated to best represent a road section at the study site. An implementation example of preventive measures is introduced and its outcome is evaluated.