An analytical method for the simultaneous determination of the four most detected non-steroidal anti-inflammatory drugs (NSAIDs) in wastewater, namely ibuprofen (IBF), naproxen (NPX), diclofenac (DFC) and ketoprofen (KFN), was developed based on gas chromatography-mass spectrometry (GC-MS). Extraction from wastewater samples was performed by solid-phase extraction (SPE) with C18 cartridges, while meclofenamic acid (MFC) was used as surrogate. The optimisation of SPE procedure included the type of the extraction solvent used for the elution and the pH of the loading solution (acidic or neutral). The developed extraction procedure resulted in good repeatability and reproducibility with relative standard deviations (RSDs) less than 10% for all the compounds. Moreover, satisfactory recoveries (>98%) were obtained. Chromatographic analysis was achieved after derivatisation with bis(trimethylsilyl) trifluoroacetamide (BSTFA) and 1% trimethyl chlorosilane (TMCS) in the presence of pyridine, a derivatisation mixture used for the first time for these compounds. The limits of detection (LODs) of the method varied from 0.37 (KFN) to 3.1 ng L-1 (NPX). The analytical method was successfully applied for the determination of these compounds in the raw and treated wastewater of two different wastewater treatment plants (WWTPs) of the city of Mytilene in Lesvos, Greece. The maximum concentrations were detected in raw wastewater originated from a hospital and they were 574 ng L-1 and 704 ngL-1 for IBF and KFN, respectively.