Purpose Sedimentary aquifers are prone to anthropogenic disturbance. Measures aimed at mitigation or adaptation require sound information on the reactivity of soil/sediments towards the infiltrating water, as this determines the chemical quality of the groundwater and receiving surface waters. Here, we address the issues of relevant sediment properties, adequate analytical methods, borehole location selection, detail of stratification, and required sample size, to develop a protocol for efficient characterization of subsurface reactivity on a regional scale. Materials and methods The sequence of geological formations in the Dutch part of the North Sea Basin is documented in the form of systematic descriptions of some 450,000 borings. The basic data are stored in a database that also includes a limited amount of geochemical data collected for specific research projects. Based on the borehole descriptions, a Digital Geological Model of the Netherlands (DGM) has recently been completed. We combined the results of a statistical analysis of the existing geochemical data with theoretical and practical considerations, to assess the degree of variability of subsurface reactivity, the relevance of different DGM-based stratifications, and the efficiency and possible redundancy of analytical parameters. Results and discussion We present two protocols for the quantitative characterization of the reactive properties of the soil and subsurface sediments of the Netherlands, down to a depth of about 30 m below surface level. As numerous strategies are already available for soil surveying, the facies-based protocol for boring and sampling is aimed at subsoil sediments. Stratification is a combination of regional, lithological, and lithostratigraphical classifications. Selection of borehole locations and sampling depths is first based on the a priori information. Given the results of the first round, additional boring, sampling and analysis are performed when necessary. The analytical protocol also applies to soil surveys. It deploys limited means to obtain the most relevant information on subsurface reactivity in view of the priority environmental issues identified. Conclusions With the progress of technologies for aquifer architecture characterization and routine chemical analysis, assessment of subsurface reactivity on a regional scale has now become feasible. Lithological stratification is essential, but regional and lithostratigraphical variability cannot be ignored. With adequate stratification, a sample size of 45 per stratum was found sufficient in most instances. The key analytes chosen appear to be statistically independent; hence, a further reduction in analytical techniques would result in serious loss of information.