Gas chromatography (GC) is a reproducible, robust, selective and sensitive method to analyse volatile organic compounds (VOCs) in a wide range of applications. The separated analytes are generally characterised by mass spectrometry (MS) under vacuum conditions. The main ionisation method is the Electron Ionisation (EI): high energy exchanges occur, causing reproducible molecular fragmentations. Chemical Ionisation (CI) is another ionisation method where a reactive gas (i.e. methane or ammonia) is ionised to form reactant ions. GC-MS can also be conducted under atmospheric pressure. Atmospheric Pressure PhotoIonisation (APPI) is the most recent source [1]. Emitted photons give rise to quasi-molecular ions. In our research platform, we recently coupled a GC Trace 1310 to a High Resolution Mass Spectrometer (HRMS) Orbitrap Fusion (ThermoScientific) with the APPI source developed by Mascom (Bremen, Germany). In this work, first, we present a general overview of the technical developments carried out on 13 VOCs with the GC-APPI-HRMS hyphenated technique. Secondly, we compare the three ionisation methods listed above. For this purpose, we used 6 VOCs of different chemical classes to determine the Limit Of Detection (LOD) for each source. Positive detection in the Orbitrap allows a factor 2 to be gained in sensitivity. In MS2, High Collision Dissociation (HCD) is more informative than Collision-Induced Dissociation (CID). For the source parameters, it is better to decrease the sheath gas flow and the transfer tube temperature to 150°C in order to enhance the MS signal. The LOD reached for each VOC depends on the chemical class of the molecule. EI is the most sensitive method to characterise acids (0.03 ppm), alcohols (0.006 ppm), ketones and esters (0.003 ppm) while CI with methane as reactant gas is more appropriate for aldehydes (0.008 ppm). Even if GC-APPI-HRMS is not the most sensitive method (from 0.004 to 0.3 ppm), the LOD ranges found in our experiments is generally better than in the literature [2]. The developments in GC-APPI-HRMS are still in progress. (1) Reducing fragmentations and enhancing sensitivity by using acetone as a dopant gas, (2) conducting in vivo analyses, are our main objectives before transferring this very promising technology to aroma compounds characterisation in food extracts or in exhaled breath.