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Counterdrug interdiction efforts designed to seize or disrupt cocaine shipments between South American source zones and US markets remain a core US “supply side” drug policy and national security strategy. However, despite a long history of US-led interdiction efforts in the Western Hemisphere, cocaine movements to the United States through Central America, or “narco-trafficking,” continue to rise. Here, we developed a spatially explicit agent-based model (ABM), called “NarcoLogic,” of narco-trafficker operational decision making in response to interdiction forces to investigate the root causes of interdiction ineffectiveness across space and time. The central premise tested was that spatial proliferation and resiliency of narco-trafficking are not a consequence of ineffective interdiction, but rather part and natural consequence of interdiction itself. Model development relied on multiple theoretical perspectives, empirical studies, media reports, and the authors’ own years of field research in the region. Parameterization and validation used the best available, authoritative data source for illicit cocaine flows. Despite inherently biased, unreliable, and/or incomplete data of a clandestine phenomenon, the model compellingly reproduced the “cat-and-mouse” dynamic between narco-traffickers and interdiction forces others have qualitatively described. The model produced qualitatively accurate and quantitatively realistic spatial and temporal patterns of cocaine trafficking in response to interdiction events. The NarcoLogic model offers a much-needed, evidence-based tool for the robust assessment of different drug policy scenarios, and their likely impact on trafficker behavior and the many collateral damages associated with the militarized war on drugs.