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In this paper, we study medium access control (MAC) protocol design for distributed cooperative wireless networks. We focus on beneficial node cooperation by addressing two fundamental issues of cooperative communications, namely when to cooperate and whom to cooperate with, from a cross-layer protocol design perspective. In the protocol design, taking account of protocol overhead we explore a concept of cooperation region, whereby beneficial cooperative transmissions can be identified. We show that a rate allocation in the cooperation region provides higher link utilization than in a non-cooperation region. To increase network throughput, we propose an optimal grouping strategy for efficient helper node selection, and devise a greedy algorithm for MAC protocol refinement. Analysis of a successful transmission probability with cooperative or direct transmission is presented. Simulation results show that the proposed approach can effectively exploit beneficial cooperation, thereby improving system performance. Further, analytical and simulation results shed some light on the tradeoff between multi-user diversity gain at the physical layer and the helper contention overhead at the MAC layer.