In this paper, modeling and simulation of high-pressure urea synthesis loop has been studied. The extended electrolytic UNIQUAC equation has been used to describe the non ideality of liquid phase of NH3–CO2–H2O–urea system under high pressure and high temperature, and the perturbed-hard-sphere (PHS) equation of state has been used to predict the vapor fugacity coefficients. The vapor–liquid equilibrium has been treated simultaneously with chemical reactions due to the complex features of the urea synthesis system. A concrete procedure for simulation of the key units and flowsheet of the high-pressure urea synthesis loop has been developed. The equilibrium-stage model has been applied to modeling and simulation of the urea reactor, CO2 stripper and other key units in the high-pressure loop for urea synthesis, and the simultaneous modular approach has been adopted to simulate the flowsheet. The simulation results have been found to be in good agreement with the design data from the industry-scale plant. This work provides an effective tool and significant guidance for design or retrofit of urea synthesis process.