The bifunctional isomerization reaction of long-chain n-alkanes to mono-branched isomers is of great interest, as the cold flow properties can be enhanced considerably. In this regard, the isomerization of n-decane on mesoporous bifunctional catalysts was studied using design of experiments. The presented application of an advanced combinatorial design reduced the required experimental testing significantly. The simultaneously varied parameters included pore and channel dimensions of the mesoporous silica support, surface acidity, noble metals and a combination of two additional metals in varying concentrations. The identification of those parameters with highest influence on selectivity and conversion permitted the detailed interpretation and subsequent optimization of the isomerization reaction. The respective support material and its surface acidity are the major driving force for conversion. High acidity increases conversion considerably and does not necessarily diminish selectivity to desired products. Changes concerning the support material may boost activity of the final catalyst sample, yet at the expense of high selectivity. This deleterious effect on selectivity can be counteracted to a considerable degree by adding small amounts of Nb. (C) 2012 Elsevier Ltd. All rights reserved.