Both fumed silica and sepiolite have been used as a filler of polyurethane (PU) adhesives. Although effective, the small particle size and the relative high cost of fumed silica are limitations in some applications. Sepiolite is cheaper than fumed silica, but its relatively large particle size facilitates its settling from the adhesive solutions. In this study, the usefulness of using sepiolite of fumed silica mixtures as a filler in solvent-based PU adhesives is demonstrated. The rheological and adhesion properties of the PU adhesive solutions and the theological and mechanical properties of the PU films (without solvent) were studied. SEM micrographs of PU films showed the morphology and compatibility of the fillers with the PU matrix. The use of sepiolite + fumed silica mixtures inhibited the settlement of the fillet from the PU adhesive solutions, increased both the storage and the loss moduli, and improved the theological and mechanical properties of the PU. On the other hand, the green (immediate) T-peel strengths of roughened styrene-butadiene rubber/PU adhesive joints and plasticized PVC/PU adhesive joints were greatly improved in filled PU adhesives. The effects produced by using fumed silica alone or sepiolite + fumed silica mixtures were very similar, although in general, somewhat more marked in fumed silica-filled PU.