Veterinary antibiotics and steroid hormones can be present at low levels in soil. Analytical methodologies are therefore necessary to analyse these compounds at the trace level in such a complex matrix. The goal of this work was to compare Pressurised Liquid Extraction (PLE), which is usually used to extract drugs from soil, and a modified-QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. Furthermore, several clean-up methods were evaluated. Selective Pressurised Liquid Extraction (SPLE) and Dispersive Solid Phase Extraction (dSPE) used after PLE and QuEChERS, respectively, were tested. These techniques permit a fast and simple purification step. SPE, which is frequently used, was also evaluated. To perform this comparison, both recoveries and matrix effects were compared and the analyses were performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). SPLE and dSPE did not significantly decrease matrix effects. A tandem SPE using SAX and Strata-X cartridges offered the best efficiency. Regarding the comparison between PLE and QuEChERS, the modified-QuEChERS led to better recoveries for certain substances. No significant differences were noted in term of matrix effects. Therefore, the modified-QuEChERS method is recommended.