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In this study the compressive cyclic behavior of bovine cancellous bone and three open-cell metallic foams including AlSi7Mg foams (30 and 45 ppi) and CuSn12Ni2 foam (30 ppi) has been investigated. Multi-step fatigue tests are carried out to study the deformation behavior under increasing compressive cyclic stresses. Short multi-step tests, with steps of 300–500 cycles, are used to identify the cyclic yield stress (σcy) and the stress at failure (σfail). The residual strain accumulation, or cyclic creep, is observed during these tests. Long multi-step tests, with 5000 cycles at selected stress ranges (0.4σcy, 0.6σcy, 0.8σcy, and σcy), are also carried out to study further the compressive fatigue behavior of the materials. Scanning electron microscopy (SEM) has been used to characterize the microstructure of the foams and the bone prior to and post mechanical testing. Particular attention is paid to the role of cyclic creep and buckling in the failure processes. The results show that residual strain accumulation seems to be the predominant driving force leading to failure of foams and bones. Although foams and bone fail by the same mechanism of cyclic creep, the deformation behavior at the transient region of each step is different for both materials. The maximum strain εmax of foams decrease suddenly during the change of each step. This behavior may be explained by the rapidly developing microdamage in the cell struts that occur at the transient region of each step. Bones show more gradual decrease of εmax, where microdamage may be accumulated progressively during the fatigue test.