A method for the simultaneous determination of 20 psychoactive drugs in pork by solid phase extraction coupled with ultra performance liquid chromatography with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was established. The samples were extracted with alkalified acetonitrile, and then cleaned up using solid phase extraction with an Oasis MCX column. The UPLC separation was performed on a C18 column (50 mm x 2.1 mm, 1.7 microm) using a gradient elution with the mobile phases of 0.1% (v/v) formic acid in water and acetonitrile. The ESI-MS/MS detection was achieved in positive mode under multiple reaction monitoring (MRM) mode. The calibration curves showed good linearity in the range of 5-100 microg/L with the correlation coefficients more than 0.99 for the 20 psychoactive drugs. The limits of quantification (LOQ, S/N > or = 10) for the 20 psychoactive drugs were 5 microg/kg. The average recoveries of the 20 psychoactive drugs spiked in blank pork at three levels of 5, 10 and 50 microg/kg were 66.8%-97.2% with the relative standard deviations from 4.2% to 12.4%. The meth od is suitable for the simultaneous determination of the 20 psychoactive drugs in pork with the characteristics of easy operation, high accuracy and precision.