Puerto Rico Highway 181 (PR-181), also known as Expreso Trujillo Alto, is a road that connects the towns of San Juan, Puerto Rico in the north/northeast coast of Puerto Rico with Patillas in the southeast, passing through the municipalities of San Juan at Jesus de Piñero Avenue (PR-17) as it approaches the Teodoro Moscoso Bridge and the Luis Muñoz Marín International Airport, Trujillo Alto, Gurabo, San Lorenzo, Yabucoa and Patillas in the center of the town district near PR-3. Along with PR-10, PR-149, PR-1 and PR-52, it is one of the longest highways crossing the island from north to south through the central mountainous region. In the north part of Trujillo Alto it is a four-lane highway, turning completely rural on the way to Patillas with the exception of a small tract in Gurabo where it intersects PR-30.

Trujillo Alto is a town and municipality of Puerto Rico located in the Northern Coastal Plain, on the boundary between the karst zone and Sierra de Luquillo, north of Caguas, and Gurabo; southeast of San Juan, and west of Carolina. Trujillo Alto is part of the San Juan Metropolitan Area, which includes the municipalities of Bayamón, Guaynabo, Cataño, and Toa Baja. The city is spread over 6 barrios and Trujillo Alto Pueblo. It is part of the San Juan-Caguas-Guaynabo Metropolitan Statistical Area.