Two different analytical methods for the determination and confirmation of ochratoxin A (OTA) in blood serum, kidney, and liver of pigs have been compared. Sample cleanup was based on liquid-liquid phase extraction. The detection of OTA was accomplished with high-performance liquid chromatography (HPLC) combined either with fluorescence detection (FLD) or electrospray ionization (ESI+) tandem mass spectrometry (MS/MS). The comparative method of evaluation was based on the investigation of 90 samples of blood serum, kidney, and liver per animal originating from different regions of Serbia. The analytical results are discussed in view of the respective method validation data and the corresponding experimental protocols. In general, analytical data obtained with liquid chromatography (LC)-MS/MS detection offered comparable good results in the sub-ppb concentration level indicating that the electrospray tandem mass spectrometric (LC-MS/MS) method was more selective and sensitive for the analysis and confirmation of OTA in pig tissues than the HPLC method after the methylation of OTA.