Initial fixation of press-fit implants depends on interference fit, surface morphology, and bone material properties. To understand the biomechanical effect of each factor and their interactions, the pull-out strength of seven types of CoCrMo tapered implants, with four different interference fits, three different surface morphologies (low, medium and high roughness), and at two time points (0 and 30 min) were tested in trabecular bone with varying density. The effect of interference fit on pull-out strength depended on the surface morphology and time. In contrast with our expectations, samples with a higher roughness had a lower pull-out strength. We found a similar magnitude of bone damage for the different surface morphologies, but the type of damage was different, with bone compaction versus bone abrasion for low and high frictional surfaces, respectively. This explains a reduced sensitivity of fixation strength to bone mineral density in the latter group. In addition, a reduction in fixation strength after a waiting period only occurred for the low frictional specimens. Our study demonstrates that it is essential to evaluate the interplay between different factors and emphasizes the importance of testing in natural bone in order to optimize the initial stability of press-fit implants.