Establishing and interpreting patterns of lithic assemblage variability is of great interest to archaeologists as they shed light on cultural adaptations in the deep past. Nowhere has this topic provoked more interest and debate than in the Middle Palaeolithic of southwestern France. The region's rich archaeological record has produced numerous sites, many of which have been recently excavated and thus provide a reliable dataset for better structuring Mousterian lithic variability. Researchers working with these types of datasets frequently employ the chaîne opératoire concept to approach lithic assemblage variability; however, the validity of such analyses has recently been questioned. Here we present results of a combined quantitative and qualitative technological analysis of a large sample of assemblages from numerous well-contextualised sites in the northeastern Aquitaine Basin. We selected clearly identifiable diagnostic elements typical of different flake production systems that can be quantified by different analysts in a replicable fashion. Our results show strong differences in assemblage composition in terms of dominant production systems as well as a smaller number of mixed assemblages that combine two or more flake production methods. When considered together, these results provide not only a means for defining lithic technocomplexes and subsequently comparing assemblages but also for investigating elements of Neanderthal material culture variability.