Traffic congestion and the resulting socio-economic losses, air pollution, etc. have been the pivotal factors that hinders the development of many cities. It is essential to develop route guidance to provide drivers with optimal routes to the destinations with a low congestion and a great road capacity to alleviate traffic congestion on the road network. This paper proposed a novel route guidance algorithm for individuals based on the connected vehicle (CV) in the vehicle infrastructure cooperative environment, providing drivers with real-time route selection, thereby alleviating the congestion of the road network, more importantly, realized the route guidance for individuals through microscopic traffic simulation software, VISSIM, and VISSIM COM interfaces, and evaluate the effects and influencing factors of individual route guidance. The methodology first developed an application program to analyze the road network, which could obtain any specified number of alternate route sets. Then, the method for judging whether the road is congested based on the average travel speed of the road segment was further proposed, detecting the network operation conditions in real time. The optimal route would be provided to drivers using the multiply logit models when there is a congested road segment of the route from the perspective of global optimization. Subsequently, compared with the VMS guidance method and based scenario, the algorithm was evaluated based on the microscopic traffic simulation software, VISSIM, and VISSIM COM interfaces, from the effectiveness of critical routes as well as overall network levels. Results indicated that the CV algorithm can improve the travel efficiency from the critical routes and overall road network levels effectively. Furthermore, the sensitivity analysis of CV permeability presented that the CV algorithm is of great significance to improve traffic effectiveness of the road network, even in the case of low CV penetration.