Bioactive Glass (BAG) granules are osteoconductive and possess unique antibacterial properties for a synthetic biomaterial. To assess the applicability of BAG granules in load-bearing defects, the aim was to compare mechanical behaviour of graft layers consisting of BAG granules and morselized cancellous bone allograft in different volume mixtures under clinically relevant conditions.The graft layers were mechanically tested, using two mechanical testing modalities with simulated physiological loading conditions: highly controllable confined compression tests (CCT) and more clinically realistic in situ compression tests (ISCT) in cadaveric porcine bone defects. Graft layer impaction strain, residual strain, aggregate modulus, and creep strain were determined in CCT. Graft layer porosity was determined using micro computed tomography. The ISCT was used to determine graft layer subsidence in bone environment.ANOVA showed significant differences (p<0.001) between different graft layer compositions. True strains absolutely decreased for increasing BAG content: impaction strain −0.92 (allograft) to −0.39 (BAG), residual strain −0.12 to−0.01, and creep strain −0.09 to 0.00 respectively. Aggregate modulus increased with increasing BAG content from 116 to 653 MPa. Porosity ranged from 66% (pure allograft) to 15% (pure BAG). Subsidence was highest for allograft, and remarkably low for a 1:1 BAG-allograft volume mixture.Both BAG granules and allograft morsels as stand-alone materials exhibit suboptimal mechanical behaviour for load-bearing purpose. BAG granules are difficult to handle and less porous, whereas allograft subsides and creeps. A 1:1 volume mixture of BAG and allograft is therefore proposed as the best graft material in load-bearing defects.