Aiming at the approximate error of commonly used methods on calculation of hydrostatic pressures of closed hydrostatic guideways with multiple pockets, a more accurate solution is proposed. Taking design of beam & slide-rest guideways for a heavy duty CNC vertical turning mill as an example, under an assumption that stiffnesses of guideways and their jointing structure are sufficiently large, the pressures of the pockets can be attained by adding a co-planarity equation that constrains pocket centers. Then, an optimization model is built to minimize the highest pocket pressure under additional constraints that are posed on the highest seal margin pressure, the highest levitating pressure of the pockets, and the maximum deformation of the guideways. The optimization problem is solved sequentially by using the methods of design of experiments and adaptive simulated annealing on iSIGHT software platform. The results show significant improvements to the original design. Optimized maximum hydrostatic pressure meets the requirement of hydraulic system.