In this research project, a route-based signal preemption strategy was developed to provide the most efficient and safe route for an emergency vehicle (EV) under a given network and traffic conditions. It combines an on-line route selection procedure and a dynamic sequential preemption method. The on-line route selection module first quantifies the level of congestion for each link on a given network using a congestion index and finds the least congested route for a given origin/destination pair using the well-known Dijkstra's algorithm. Further it also selects the safest signal phase for each intersection for a given travel direction of an EV. Once an emergency route is selected, the dynamic preemption module starts the preemption of the signals on the emergency route sequentially considering the location of the EV and the state of signal phase for each intersection. By sequentially preempting the traffic signals on a route with advance activation, the proposed strategy tries to clear the traffic queue for an EV approaching each intersection. The evaluation results with pre-specified emergency routes show a 10 to 16% reduction of the emergency vehicle travel time for relatively long and/or complicated routes compared with the existing intersection-by-intersection preemption method. Further, the network-wide performance measures with the dynamic preemption method were very compatible with those from the existing intersection-by-intersection clearance method.