The selectivity performance of an upflow fixed-bed reactor was optimized for the exothermic consecutive hydrogenation of 1,5,9-cyclododecatriene (CDT) to cyclododecene (CDE) over 0.5% Pd/alumina. The influence of the main operating variables (temperature, hydrogen pressure, and liquid and hydrogen flow rates) on global hydrogen conversion and CDE selectivity was studied and analyzed. The reactor performance obtained for a pellet catalyst was shown to be sensitive to external mass transfer of the gaseous reactant and backmixing in the liquid phase. The surface concentration of hydrogen was found to be the key parameter because of its opposite effect on the rate of hydrogenation and selectivity. Increasing the gas velocity provided a higher hydrogen concentration at the catalyst surface, enhancing the global rate of hydrogenation, although an increase in the global hydrogen conversion was always related to a reduction of CDE selectivity. When the liquid velocity was decreased, backmixing became important in the liquid phase, also resulting in a loss of selectivity. To improve the reactor performance in terms of selectivity, process staging and hydrogen dilution by an inert gas were tested. Both, but in particular the split-up of the process into several stages, proved to be successful in obtaining high yields of CDE up to 90%, required for industrial application.