FREDERICK, Md.—Officials in Pennsylvania, Maryland, Virginia and North Carolina are beefing up enforcement of U.S. Route 15 to reduce crashes along 400 miles of the thoroughfare popular with vacationers trying to avoid congested interstates.

During "Operation Border to Border," which runs from Friday through Sunday, agencies in the four states will work together to conduct saturation patrols, sobriety check points and other enforcement initiatives. They hope to reduce the number of traffic crashes and combat criminal behavior along the highway that runs through the four states.