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We present a progressive approximation algorithm for the exact solution of several classes of interdiction games in which two noncooperative players (namely an attacker and a follower) interact sequentially. The follower must solve an optimization problem that has been previously perturbed by means of a series of attacking actions led by the attacker. These attacking actions aim at augmenting the cost of the decision variables of the follower’s optimization problem. The objective, from the attacker’s viewpoint, is that of choosing an attacking strategy that reduces as much as possible the quality of the optimal solution attainable by the follower. The progressive approximation mechanism consists of the iterative solution of an interdiction problem in which the attacker actions are restricted to a subset of the whole solution space and a pricing subproblem invoked with the objective of proving the optimality of the attacking strategy. This scheme is especially useful when the optimal solutions to the follower’s subproblem intersect with the decision space of the attacker only in a small number of decision variables. In such cases, the progressive approximation method can solve interdiction games otherwise intractable for classical methods. We illustrate the efficiency of our approach on the shortest path, 0-1 knapsack and facility location interdiction games. Summary of Contribution: In this article, we present a progressive approximation algorithm for the exact solution of several classes of interdiction games in which two noncooperative players (namely an attacker and a follower) interact sequentially. We exploit the discrete nature of this interdiction game to design an effective algorithmic framework that improves the performance of general-purpose solvers. Our algorithm combines elements from mathematical programming and computer science, including a metaheuristic algorithm, a binary search procedure, a cutting-planes algorithm, and supervalid inequalities. Although we illustrate our results on three specific problems (shortest path, 0-1 knapsack, and facility location), our algorithmic framework can be extended to a broader class of interdiction problems.