An ultra performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap) was developed for the rapid screening and confirmation of 74 antibiotics and other compounds in swine urine.The samples were high speedily centrifuged,then diluted with solvent,and finally separated on an Agilent SB C18 (3.0 mm×100 mm，1.8 μm) column using a binary solvent system composed of 0.1% formic acid aqueous solution and 0.1%formic acid acetonitrile solution by gradient elution.Under the optimal conditions,the analytes were precisely screened and confirmed with the precision mass,retention time and two stage ion mass spectra．There were good linear relationships for 74 analytes in their respective concentration ranges with correlation coefficients(r2) larger than 0.99 and limits of detection(LOD) of 10 ng/mL.The recoveries for 74 compounds in swine urine at LOD spiked level mainly ranged from 55.8%to 120%,with relative standard deviations(RSD) of 1.3%-21%.The method was convenient，rapid，sensitive and accurate,and was quite effective for the screening and confirmation of 74 antibiotics and other compounds in swine urine,which was beneficial to the investigation on drugs situation in husbandry.