Groundwater sampling in boreholes has been carried out for decades according to well-established protocols and regulations. An important requirement in this context is the need to purge the borehole prior to any sampling action, the volume of the purge being adapted to the water flow and the regulatory context. Contaminated site investigations have introduced the concept of water column heterogeneity in the screened section of boreholes, which also occurs in some uncontaminated boreholes or in long-screened boreholes. Specific guidelines and practices were thus introduced, in particular the concept of discrete sampling. This type of sampling can be advantageously used in deep boreholes, provided that there is some renewal of water at the screens or the perforated intervals. The present study aims to take a step forward in the characterization of deep boreholes set up in the Aquitaine basin in France, by defining a protocol for relatively short boreholes (depth < 170 m) and applying it to much deeper boreholes, formerly drilled for oil and gas exploration (sampling up to 1035 m deep). Acquisitions were performed to better characterize water chemistry, including some isotope considerations. They were based on physico-chemical logging and endoscopic inspections where technically possible. After a review of the information provided by the investigations on the characterization of the Paleocene – Eocene aquifer in southwestern France, a methodology is proposed to make sampling in deep boreholes with low-yield more reliable, by combining the abstraction of a reduced water volume and the use of a downhole sampling system.