This paper investigates the application of a Bottoming Cycle (BC) applied to a 10-litre (L) heavy duty Diesel engine for potential improvements in fuel efficiency. With the main thermodynamic irreversibility in the BC due to the temperature difference between the heat source and the working fluid, a proper selection of the working fluid and its operating condition for a given waste heat is the key in achieving high overall conversion efficiency. The paper reviews a fluid selection methodology based on thermodynamic/thermo-physical and environmental/safety properties. Results are presented using seven pure, dry, isentropic and wet working fluids (synthetic, organic and inorganic) operating with expansion starting from the saturated vapour, superheated vapour, supercritical phase, saturated liquid, and two-phase. Efficiency improvements by recovering Charge Air Coolers (CAC) and Exhaust Gas Recirculation (EGR) cooler heat on two engine platforms were calculated. The first platform operating at Euro 6 engine out NOx emissions levels and the second platform operating with Euro 5 engine out NOx emissions coupled with a 80% efficient selective catalytic reduction system. Performance and heat rejection data for the 10L platforms were derived from experimental measurements on an advanced 2L single cylinder research engine which was used to determine the trade-off between thermal efficiency and regulated/unregulated emissions. Results indicate a potential improvement of 5.1% and 6.3% in engine power for a cruise (B50) and high load (C100) condition, with a technically feasible BC operating at subcritical mode with minimum superheat.