Sedimentation affects the safety of reservoir flood control and the profit of reservoir operation. Project safety and the cost and benefit of dredging are the priority factors of reservoir dredging decision-making. Aiming at two major reservoir sedimentation management methods of dam heightening or mechanical dredging, a dredging decision-making model is established by introducing the engineering safety factor and the profit factor. The engineering safety factor is characterized by the ratio of dam failure probability decrease through each sedimentation management method and the profit factor is characterized by the ratio of each method’s payback period. The weight coefficients in the decision-making method are determined by linear regression analysis based on massive engineering data collected from real project sedimentation cases. In terms of different degree of influence on engineering safety by sedimentation, the dredging decision-making model could be simplified as a single factor model. This model is then applied for Nanying Reservoir dredging project in Gansu Province and the mechanical dredging decision is made which verifies its practicability and rationality. This study could provide a scientific method for decision-making of reservoir dredging at national level in the future.