Vitacel M80K, a cellulose powder coated with 2% colloidal silica, is a recently developed direct compressible vehicle (DCV). The aim of this study is to investigate the performance of M80K, in comparison with: a laboratory prepared vehicle (ELC+) consisting of a mixture of Elcema P050 (ELC) and 2% Aerosil, and a microcrystalline cellulose (MCC), Avicel PH 101 (Avicel). Bulk density, flow and surface characteristics of the DCVs were determined. Tablets were prepared by direct compression using various drugs; ascorbic acid (fine and coarse crystals), cimetidine, and paracetamol. Tablets prepared with M80K showed less weight variation than those prepared with Avicel. Ascorbic acid-Avicel tablets were slightly harder than those with M80K. However, in the presence of either cimetidine or paracetamol, M80K resulted in the production of tablets with maximum hardness. In most cases, except with paracetamol, M80K produced tablets with slightly higher friability in comparison to Avicel, while ELC+ showed maximum friability. M80K-paracetamol tablets showed the minimum friability values and highest hardness sensitivity towards increase of the applied compression force between 5 and 35 kN. M80K-containing formulations showed better hardness tolerance upon the addition of magnesium stearate. Disintegration times for most tablets were relatively short (<5 min).