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AbstractPurpose -The purpose of this paper is to introduce efficient methods for solving the 2D biharmonic equation with Dirichlet boundary conditions of second kind. This equation describes the deflection of loaded plate with boundary conditions of simply supported plate kind. Also it can be derived from the calculus of variations combined with the variational principle of minimum potential energy. Because of existing fourth derivatives in this equation, introducing high-order accurate methods need to use artificial points. Also solving the resulted linear system of equations suffers from slow convergence when iterative methods are used. This paper aims to introduce efficient methods to overcome these problems. Design/methodology/approach -The paper considers several compact finite difference approximations that are derived on a nine-point compact stencil using the values of the solution and its second derivatives as the unknowns. In these approximations there is no need to define special formulas near the boundaries and boundary conditions can be incorporated with these techniques. Several iterative linear systems solvers such as Krylov subspace and multigrid methods and their combination (with suitable preconditioner) have been developed to compare the efficiency of each method and to design powerful solvers. Findings -The paper finds that the combination of compact finite difference schemes with multigrid method and Krylov iteration methods preconditioned by multigrid have excellent results for the second biharmonic equation, and that Krylov iteration methods preconditioned by multigrid are the most efficient methods. Originality/value -The paper is of value in presenting, via some tables and figures, some numerical experiments which resulted from applying new methods on several test problems, and making comparison with conventional methods.