Currently available data on the Pleistocene human occupation of the westernmost territories of Iberia attest to the presence of Middle Palaeolithic industries from c. 240 ka cal bp until c. 37 ka cal bp. Previous studies focusing on this time frame have suggested that Middle Palaeolithic populations were highly mobile and predominately utilised locally available raw materials, with many cave and open-air sites being located near fluvial settings. Other than these observations, no specific studies have focused on exploring the factors influencing human site location choice during that time range. Employing statistical and GIS approaches, this paper provides an initial assessment of spatial patterning in human settlement during the Middle Palaeolithic of westernmost Iberia. Results show that site locations are biased towards lower elevations and riverine settings and suggest that distance to rivers might have impacted the diversity and specific types of lithic raw materials used at each site. These results help to shed light on the particularities of Neanderthal adaptations in a region regarded as a refugium during periods of unfavourable climate during the Middle Palaeolithic.