Abstract. Due to its dryness, the subtropical free troposphere plays a critical role in the radiative balance of the Earth's climate system. But the complex interactions of the dynamical and physical processes controlling the variability in the moisture budget of this sensitive region of the subtropical atmosphere are still not fully understood. Stable water isotopes can provide important information about several of the latter processes, namely subsidence drying, turbulent mixing, and dry and moist convective moistening. In this study, we use high-resolution simulations of the isotope-enabled version of the regional weather and climate prediction model of the Consortium for Small-Scale Modelling (COSMOiso) to investigate predominant moisture transport pathways in the Canary Islands region in the eastern subtropical North Atlantic. Comparison of the simulated isotope signals with multi-platform isotope observations (aircraft, ground- and space-based remote sensing) from a field campaign in summer 2013 shows that COSMOiso can reproduce the observed variability of stable water vapour isotopes on timescales of hours to days, thus allowing us to study the mechanisms that control the subtropical free-tropospheric humidity. Changes in isotopic signals along backward trajectories from the Canary Islands region reveal the physical processes behind the synoptic-scale isotope variability. We identify four predominant moisture transport pathways of mid-tropospheric air, each with distinct isotopic signatures: air parcels originating from the convective boundary layer of the Saharan heat low (SHL) – these are characterised by a homogeneous isotopic composition with a particularly high δD (median mid-tropospheric δD=-122‰), which results from dry convective mixing of low-level moisture of diverse origin advected into the SHL; air parcels originating from the free troposphere above the SHL – although experiencing the largest changes in humidity and δD during their subsidence over West Africa, these air parcels typically have lower δD values (median δD=-148‰) than air parcels originating from the boundary layer of the SHL; air parcels originating from outside the SHL region, typically descending from tropical upper levels south of the SHL, which are often affected by moist convective injections from mesoscale convective systems in the Sahel – their isotopic composition is much less enriched in heavy isotopes (median δD=-175‰) than those from the SHL region; air parcels subsiding from the upper-level extratropical North Atlantic – this pathway leads to the driest and most depleted conditions (median δD=-255‰) in the middle troposphere near the Canary Islands. The alternation of these transport pathways explains the observed high variability in humidity and δD on synoptic timescales to a large degree. We further show that the four different transport pathways are related to specific large-scale flow conditions. In particular, distinct differences in the location of the North African mid-level anticyclone and of extratropical Rossby wave patterns occur between the four transport pathways. Overall, this study demonstrates that the adopted Lagrangian isotope perspective enhances our understanding of air mass transport and mixing and offers a sound interpretation of the free-tropospheric variability of specific humidity and isotope composition on timescales of hours to days in contrasting atmospheric conditions over the eastern subtropical North Atlantic.