Worldwide, maritime trade accounts for approximately 80% of all trade by volume and is expected to double in the next twenty years. Prior to September 11, 2001, Ports, Waterways and Coastal Security (PWCS) was afforded only 1 percent of United States Coast Guard (USCG) resources. Today, it accounts for nearly 22 percent of dedicated USCG resources. Tactical assessment of resource requirements and operational limitations on the PWCS mission is necessary for more effective management of USCG assets to meet the broader range of competing missions. This research effort involves the development and validation of a discrete-event simulation model of the at-sea vessel interdiction process utilizing USCG deepwater assets. A discrete-event simulation model of the interdiction, control and boarding, and inspection processes has been developed and validated. Through a simulation optimization approach, our research utilizes the efficiency of a localized search algorithm interfaced with the simulation model to allocate USCG resources in the interception, boarding, and inspection processes with the objective of minimizing overall process time requirements. The model is tested with actual USCG data to gain insight on the development of efficient and effective interdiction operations.