A multi-residue pressurised liquid extraction (PLE) methodology has been established for the determination of the four ionophores: lasalocid, monensin, salinomycin and narasin in solid environmental matrices. The PLE methodology is combined with solid phase extraction as clean-up using liquid chromatography coupled to tandem mass spectrometry applying electrospray ionisation for detection. The samples were freeze-dried prior to extraction. The absolute recoveries for soil and sediment ranged from 71 to 123% (relative standard deviation (RSDs) below 16%) and in the range 94–133% (RSDs 9–35%) for poultry manure. The final method allowed for the detection of four ionophores down to a few hundred ng kg−1 in natural solid matrices with limit of quantifications (LOQs) being 0.96, 0.87, 0.98, and 0.64 μg kg−1 in soil for lasalocid, monensin, salinomycin, and narasin, respectively. Corresponding LOQs in sediment were 1.28, 1.34, 1.39, and 0.78 μg kg−1 for the respective ionophores, while in manure the LOQs were 0.98, 1.01, 1.45, and 1.01 μg kg−1.