Mobility management plays an important role to provide nomadic users with ubiquitous and seamless connections for prevalent real-time multimedia communication services. Predictive pre-registration (PR) in cross-layer is one of the best-known methods applied to trigger layer-3 handoff before layer-2 handoff to shorten handoff delay (the delay of roaming from one wireless domain to another). However, if the prediction is fail, PR will suffer burst packets loss and long handoff delay. In this paper, a new mobility management protocol named Opportunistic Multiple PR (OMP) is proposed to increase the success rate of both handoff prediction and handoff to better network. OMP provides a cost-effective way for pre-registering multiple wireless networks. We have tested OMP by many mobile applications including real-time multimedia VoD/VoIP on vehicles. Wireless handoff on different road intersections are evaluated by two perceptual quality indices, PSNR and MOS. Experimental results show that OMP can significantly improve QoS even with low prediction accuracy. The analytic model of OMP suggests not only thresholds for PR number, but also candidate handoff targets (CHT) in neighbor wireless networks. It can gain the maximum handoff performance in cost-effectiveness.