This paper explores the potential of wireless smart sensors for structural health monitoring of railroad bridges. The Imote2 smart sensor, combined with sensor board hardware and application-oriented software developed at the University of Illinois, forms the heart of the system. To demonstrate the efficacy of this system, wireless acceleration and strain sensors are deployed on a railroad bridge near Chicago, which is the busiest railroad hub in North America. The bridge is traversed daily by both passenger and freight traffic. Experimental data is collected for this bridge subject to in-service loads. Acceleration data was used to develop a bridge model with predictive capabilities. Wireless strain sensors attached to the rail were able to estimate train carloads and speeds for revenue traffic. Wireless magnetic strain sensors collected structural responses under trains. A work train with known loads and geometries was run over the bridge at different speeds. These results demonstrated wireless smart sensors to be a portable, cost-effective, and practical means for monitoring railroad bridges.