Two green chemistry extraction systems, an in-house stainless-steel column Pressurized Hot Water Extraction system (PHWE) and a commercially available Espresso machine were applied for analysing 23 active pharmaceutical ingredients (APIs) in sewage sludge. Final analysis was performed on UPLC-MS/MS using two different chromatographic methods: acid and basic. When analysing all 23 APIs in sewage sludge both extraction methods showed good repeatability. The PHWE method allowed for a more complete extraction of APIs that were more tightly bound to the matrix, as exemplified by much higher concentrations of e.g., ketoconazole, citalopram and ciprofloxacin. In total, 19 out of 23 investigated APIs were quantified in sewage sludge, and with a few exceptions the PHWE method was more exhaustive. Mean absolute recoveries of 7 spiked labelled APIs were lower for the PHWE method than the Espresso method. Under acid chromatographic conditions mean recoveries were 16% and 24%, respectively, but increased to 24% and 37% under basic conditions. The difference between the PHWE method and the Espresso method might be interpreted as the Espresso method giving higher extraction efficiency; however, TIC scans of extracts revealed a much higher matrix co-extraction for the PHWE method. Attempts were made to correlate occurrence of compounds in sewage sludge with chemical properties of the 23 APIs and there are strong indications that both the number of aromatic rings and the presence of a positive charge is important for the sorption processes to sewage sludge.