A new approach was established for the simultaneous determination of 29 restricted drugs,including quinolones,sulfoamides,trimethoprim,tetracyclines,lincosamides,macrolides in urine of swine supplied to Hong Kong by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The analytes were extracted with ammonium acetate and EDTA buffer,and followed by cleanup using an HLB solid phase extraction cartridge.The sample matrix-matched calibration was used to determine the residue.Electrospray ionization mass spectrometry was operated in the positive mode. The analysis of 29 restricted drugs was achieved under the multiple reaction monitoring(MRM) mode.The results indicated that correlation coefficients of the calibration curves were more than 0.99.The average recoveries of 29 analytes at three spiked concentration levels ranged from 58% to 108%.The intra-day relative standard deviations(RSDs) were in the range of 1.9%-18.9%,and the inter.day RSDs were 3.4%-20.9%.The limits of quantitations(LOQs,S/N≥10) were in the range of 1.0-10.0 μg/L.The method is economic,high efficient and reliable,and is suitable for the simultaneous determination of multiple residues of veterinary drugs in swine urine．