Heavy duty tractor-trailers under freeway operations consume about 65% of the total engine shaft energy to overcome aerodynamic drag force. Vehicles are exposed to on-road crosswinds which cause change in pressure distribution with a relative wind speed and yaw angle. The objective of this study was to analyze the drag losses as a function of on-road wind conditions, on-road vehicle position and trajectory. Using coefficient of drag (CD) data available from a study conducted at NASA Ames, Geographical Information Systems model, time-varying weather data and road data, a generic model was built to identify the yaw angles and the relative magnitude of wind speed on a given route over a given time period. A region-based analysis was conducted for a study on interstate trucking operation by employing I-79 running through West Virginia as a case study by initiating a run starting at 12am, 03/03/2012 out to 12am, 03/05/2012. Results showed that vehicles which travelled the route on 03/04/2012 after 2pm were subjected to higher yaw angles (9 - 14 degrees) compared to vehicles travelling between 12am and 2pm on the same day. Similar analysis on 03/03/2012 for the same route concluded vehicles travelling between 11:30am and 4pm were subjected to lower yaw angles (0-6 degrees) compared to vehicles travelling through the rest of the day (9 - 16 degrees). A temporal analysis revealed that CD values may vary significantly for vehicles travelling the same route but a few hours apart.