This paper presents the main industrially relevant results from a joint academic and industrial venture to develop ring-opening Pt-Ir catalysts for upgrading HDT-LCO into a high-quality diesel-blending component. The influence of the support (alumina-bound CeO2, gamma-Al2O3, and boehmite) and preparation method (microemulsion versus co-impregnation) on the physicochemical catalyst properties were studied by a variety of techniques, including XRF spectrometry, dynamic CO pulse chemisorption, TPR/TPO, XPS, HRTEM-EDX, and TPD of n-propylamine. The catalytic performance was evaluated in a pilot unit under industrially employed conditions (40 bar) with indan- and tetralin-based model feeds and the real prehydrotreated LCO, respectively. From HRTEM and XPS observations chiefly, it was deduced that microemulsion catalysts have separate Pt and Ir phases, whereas the impregnation catalyst contains an alloy type of bimetallic clusters. In all, the experimental results clearly provide evidence of the decisive role played by the active metallic component in terms of the bimetallic interaction between Pt and It upon the hydrogenolysis/ring-opening performance. Irrespective of the preparation method, the Pt5Ir95/CeO2 catalysts perform better than a commercial catalyst in terms of cetane index improvement of the HDT-LCO.