Abstract: In order to predict leak-off pressure in high-permeability sandstone formations and ensure drilling safety,through analysis of the flow characteristics of drilling fluid in mud cake zone,invaded zone and in-situ pores,two calculation models for predicting leak-off pressure were established,with or without mud cake on wellbore,according to the constitutive equation of plastic fluid and capillary percolation theory.The leak-off pressure of Well Yacheng 13-1-A15 was predicted by this model,the results indicate that leak-off pressure equivalent density was 0.613 kg/L in the case of no mud cake on the wellbore;the leak-off pressure equivalent density was 1.21 kg/L when mud cake formed on the wellbore with the thickness of 1 mm and permeability was less than 4×10-5 D.Lost circulation did not occur in the drilling of Well Yacheng 13-1-A15 through adoption of Versaclean high temperature oil-based plugging drilling fluids with a density of 1.10 kg/L.The prediction model for leak-off pressure could provide a theory basis for safe drilling in high-permeability sandstone formations.