• The magnitude of the isotope effect is determined by the pressure in the sub-divertor. • Pumping of gas within the JET divertor is effective near the outer target only. • The re-distribution of the neutrals due to drifts decreases the throughput. • The total decrease of the throughput reduces the isotope effect. Experiments in JET-ILW Ohmic confinement mode plasmas show that the line-averaged detachment onset density in deuterium discharges is approx. 10% lower than in hydrogen discharges. The magnitude of the isotope effect on the detachment onset density depends on the divertor geometry, the magnetic configuration and the throughput of the sub-divertor/divertor cryopump system. Simulations with the edge fluid code EDGE2D-EIRENE revealed that the pumping of neutral gas within the JET divertor is effective near the outer divertor target only. The studies show that the magnitude of the isotope effect is determined by the molecular pressure in the sub-divertor pumping plenum. According to the simulations, operating in vertical configurations or closer proximity of the strike point increases the molecular pressure (and thus throughput) in front of the outer pumping plenum by up to 15% compared to the horizontal configuration, thus producing a stronger isotope effect on the detachment onset density. Similarly, EDGE2D-EIRENE predicts that plasma, hence neutral, redistribution due to E × B drifts in favourable B T configurations (ion B × grad(B) towards the divertor) decreases the throughput. The total decrease of the throughput reduces the isotope effect on the detachment onset density, and decreases the detachment onset density for both isotopes.