This paper presents a mathematical model for the loop pipelining problem that considers several parameters for optimization and supports any combination of resource and timing constraints. The unrolling degree of the loop is one of the variables explored by the model. By using Farey’s series, an optimal exploration of the unrolling degree is performed and optimal solutions not considered by other methods are obtained. Finding an optimal schedule that minimizes resource and register requirements is solved by using an Integer linear programming (ILP) model. A novel paradigm called branch and prune is proposed to eficiently converge towards the optimal schedule and prune the search tree for integer solutions, thus drastically reducing the running time. This is the first formulation that combines the unrolling degree of the loop with timing and resource constraints in a mathematical model that guarantees optimal solutions.