Microbial sulfate reduction possesses a potential risk for the long-term safety of spent nuclear fuel repositories because under expected repository conditions sulfide is the main corroding agent for copper and copper-coated steel canisters foreseen in the Scandinavian disposal concepts. It is thus essential to understand and quantify the processes and factors impacting microbial sulfide production within and around compacted bentonite, which is planned to be used as a buffer material in many repository concepts. In the present study reactive transport modelling was applied to increase the understanding of diffusion cell experiments, which brought sand layers with or without inoculated microorganisms in contact with compacted and saturated bentonites of different mineralogy. Model results obtained for a sodium bentonite from Wyoming and a calcium bentonite from Bulgaria gave strong evidence for the activation of bentonite indigenous microorganisms, at least in zones of a reduced density close to the bentonite/sand interface. For all experiments, the calculations indicated that after an initial phase of favourable conditions, microbial activity was limited by the (bio-)availability of organic carbon. In the Bulgarian bentonite, characterized by a very low gypsum content, the model furthermore suggested some intermediate control of microbial sulfate reduction by sulfate availability. The present study thus demonstrated the rapid evolution of a transport limited system in settings where zones of microbial activity are in contact with highly compacted microbially-inactive bentonite. Gypsum dissolution calculated and determined experimentally for the Wyoming bentonite indicated significant gypsum dissolution in the first 2 cm from the interface during 450 days. The reactive transport model applied successfully in this study for the description of an experimental system followed the conceptual models for microbial sulfate reduction in repository settings. The results obtained offer insights regarding the mechanism and magnitude of biogeochemical reactions that might occur in the vicinity of the bentonite buffer surrounding the waste canister and in so doing, may be relevant for the near field of HLW repositories.