Transmutation of long-lived nuclear waste (trans-uranic actinides and long-lived fission products) currently stored in spent reactor fuels may represent an attractive alternative to deep geologic disposal. The aqueous-based accelerator transmutation of waste (ATW) concept as proposed by Los Alamos National Laboratory uses a proton accelerator to produce a 1.6-GeV, 250-mA (∼400 MW) beam that is split four ways and directed to four D2O-cooled solid tungsten-lead composite targets. Each target in turn is centered in a heavy water moderated, highly multiplying, actinide (oxide)-slurry blanket. High thermal-neutron fluxes are produced that allow high transmutation reaction rates at low material (actinide, long-lived fission product) inventories. The target-blanket system for ATW resides at an interface separating two major systems that are crucial to the economic and technical success of the concept: (a) the high-energy (power-intensive) accelerator delivering 0.8 to 1.6 GeV protons to the high-Z spallation neutron source and (b) the chemical-plant equipment (CPE) that provides feedstock appropriate for efficient and effective transmutation. Parametric studies have been performed to assess the effects of the target-blanket on overall system performance with regard to neutron economy, chemical-processing efficiency, and thermal-hydraulic design options. Based on these parametric evaluations, an interim base-case aqueous-slurry ATW design was selected for more detailed analyses. This base-case target-blanket consists of an array of Zr-Nb pressure tubes placed in a heavy water moderator surrounding a heavy-water-cooled tungsten-lead target. Neutronics and thermal-hydraulic calculations focusing primarily on the blanket indicate that each of the four ATW target-blanket modules operating with a neutron multiplication keff = 0.95 can transmute the actinide waste and the technetium and iodine waste from ∼ 2.5 light water reactors (LWRs). In addition, by recovering and converting the fission heat, sufficient electricity can be produced both to operate the accelerator and to supply power to the grid for revenue generation; the full (400-MW beam) system would service ∼ 10 LWRs, which at 835 MW(thermal)/ LWR (1363 mol/yr actinide), a thermal-to-electric conversion efficiency of 0.30, and an overall “wall-plug” accelerator efficiency of 0.50 would allow about two-thirds of the 2500-MW(electric) (gross) power to be delivered to the grid. The neutronics-, thermal-hydraulics-, and accelerator-CPE-interface consideration, needed to ensure this performance, is examined for the aqueous-slurry ATW. These broad-based parametric studies have provided guidance to a preliminary conceptual engineering design of the aqueous-slurry ATW blanket concept.