An efficient method is provided to detect simultaneously some important veterinary drugs from different classes in highly complex animal tissue matrix. This method using matrix solid-phase dispersion (MSPD) and high performance liquid chromatography (HPLC) with diode array detection (DAD) is developed to effectively determine two fluoroquinolones (enoxacin and lomefloxacin), two sulfonamides (sulfanilamide and sulfamethoxazole) and one tetracycline (tetracycline) simultaneously in porcine tissues. In the process, MSPD methodology was used to treat samples, washed by n-hexane to remove lipid, eluted the analytes with acetonitrile-dichloromethane (1:1, v/v). Solvent acetonitrile and solvent acetic acid (0.1%) were combined in a gradient. HPLC-DAD analysis of the tissue samples was performed within 15 min at a flow rate of 1.0 mL/min. The results showed that a recovery at 0.1, 0.5 and 1.0 μg/g fortification levels ranged from 80.6% to 99.2% with satisfactory relative standard deviations (RSDs) (below 6.1%, n=3) and the limits of quantitation (LOQ) ranged from 7 μg/kg to 34 μg/kg in porcine tissues. Utilization of the method in successfully simultaneous analysis of porcine tissue incurred with veterinary drug multiresidues is described.