The present work is a re-evaluation of previous research on the durability of hot-mix asphalt made with recycled concrete aggregates from construction and demolition waste (CDW) with a different approach. Response surface methodology (RSM) was used to conduct this study. The kind of natural aggregates (schist and calcite-dolomite), the recycled concrete aggregates percentage (0%, 20%, 40% and 60%) and the water saturation (0% and 100%) were the pertinent factors for this methodology. Indirect tensile stress (ITS) was determined in mixtures fabricated with 0%, 20%, 40% and 60% recycled concrete aggregates. According to the results, the ITS of the bituminous mixtures increases as the percentage of recycled concrete aggregate increases. This behavior is more significant when calcite-dolomite is used as a natural aggregate. Water saturation has the same influence in both natural aggregates. The indirect tensile strength ratio (ITSR) was calculated to evaluate the stripping potential. According to the Spanish specifications, the results suggest that the percentage of CDW that can be used for hot mixes is 17% when schist is used as natural aggregate and 14% for calcite-dolomite.