Pesticide residues are high on the list of consumer concerns and consequently laboratories are tasked to screen samples for as many pesticides as possible in a single analysis within an appropriate timescale. Most countries have clearly defined regulations governing pesticide residues. Legislation imposes Maximum Residue Limits (MRLs) for pesticide residues in food commodities requiring analytical techniques that are sensitive, accurate, and robust. Multi-residue analysis is challenging due to the low limits of detection required to achieve MRL compliance for a diverse range of pesticides in a wide range of food commodities. There are currently in excess of 1000 pesticides known to be in use, and laboratories are under increasing pressure to increase the scope of the analytical methods for routine monitoring purposes. Various technologies are used to meet this challenge, the most common being Liquid Chromatography (LC) and Gas Chromatography (GC) coupled to tandem quadrupole mass spectrometry. Implementation of these techniques allows the laboratory to cover a range of compounds with varying chemistries as required by legislation. In GC/MS/MS the traditional ionization mode used is Electron Impact(EI). This is a relatively “hard” ionization method and results in a high degree of analyte fragmentation, which compromises the selectivity and sensitivity of the MS/MS measurement. Atmospheric Pressure Gas Chromatography (APGC) is a “soft” ionization technique resulting in less fragmentation and subsequently increasing the sensitivity and selectivity of MS/MS methods.1 The APGC source is readily interchangeable with the electrospray (ESI) source enabling a single platform to be used for the analysis of both GC- and LC-amenable pesticides. In this application note we describe the development and validation of a highly sensitive, multi-class method for the routine determination of 142 pesticide residues in QuEChERS extracts of various fruit and vegetables using APGC and Xevo TQ-S.