The aim of this research is to study the effect of the interference level and of the coupling procedure on the shear strength of Loctite 648 anaerobic adhesive. The tests involved shaft-hub joints with a quite large interference range and joined by a broad range of coupling strategies, which is one of the main issues of novelty of this research. 42CrMo4 tempered steel shaft specimens and 16CrNi4Pb hardening steel hub samples were used. Two factors were considered: the interference level and the assembly strategy. Four different levels of specific interference were analyzed up to a maximum value of 0.22%, performing five replications per level. Experimental trials were carried out with different coupling procedures: using press-fitted and shrink-fitted joints. Using the first procedure, a high level of interference induces scratches on the sample surfaces. These are conversely not produced by shrink-fitting. Some tests were devoted to friction coefficient estimation, thus also assessing the lubricating properties of the adhesive. Particularly, dry couplings and couplings and de-couplings with not yet cured adhesive were run to address this point. The results were processed by statistical methods, to assess the influence of the studied factors on the adhesive strength.