This paper investigates the gravity disturbance compensation for inertial navigation system based on high-resolution global gravity field models. The high-precision gravity is calculated using the European Improved Gravity model of the Earth by New techniques (EIGEN)-6C4, which is a representative of the high-resolution models. The coupling effects of horizontal uncalibrated accelerometers drift bias and gravity disturbance on initial alignment and pure calculation have been analyzed in detail. It is pointed out that the gravity disturbance compensation is necessary only when the uncalibrated accelerometers drift bias is smaller than the gravity disturbance with one order of magnitude. Simulation and ship-mounted experimental results validate the theoretical analysis and conclusions.