In clinical practice, implant failure usually occurs at the biomaterial–host tissue interface, typically involving both biomechanical and biochemical mechanisms. By definition, any new ‘bioactive’ material will bond to living bone but, prior to clinical use, interface formation, performance, longevity and failure pattern characterizations are necessary. The common missing link in many biomaterial interface investigations is imaging at the point of presumed loaded failure. The novel real-time confocal technique described here allows bond strength, formation rate, longevity and bone–material interface failure pattern characterization for a wide range of biomaterials capable of forming tissue interfaces, in one real-time imaged microshear stress process, conducted using imaging frame matched load/displacement data acquisition under relatively normal near in vivo environmental conditions. The technique, validated by post-failure scanning electron microscopy imaging, revealed that more slowly reacting melt-derived 45S5 glass materials produced stronger and more stable long-term interfaces than faster reacting microporous bioactive sol-gel glasses.