Pennsylvania Route 381 (PA 381) is a 49.3-mile-long (79.3 km) state highway located in Fayette, and Westmoreland counties in Pennsylvania. The southern terminus is the West Virginia state line near , where it continues as Preston County Route 8 to its southern terminus at WV 26 in Brandonville, West Virginia. The northern terminus is at U.S. Route 30 (US 30) near Ligonier.