A contemporary approach for improving and developing the understanding of heavy-duty Diesel engine combustion processes is to use a concerted effort between experiments at well-characterized boundary conditions and detailed, high-fidelity models. In this paper, combustion processes of n-dodecane fuel sprays under heavy-duty Diesel engine conditions are investigated using this approach. Reacting fuel sprays are studied in a constant-volume pre-burn vessel at an ambient temperature of 900 K with three reference cases having specific combinations of injection pressure, ambient density and ambient oxygen concentration (80, 150 & 160 MPa-22.8 & 40 kg/m 3-15 & 20.5% O 2). In addition to a free jet, two different walls were placed inside the combustion vessel to study flame-wall interaction. Experimentally, low-and high-temperature reaction product distributions are imaged simultaneously using single-shot planar laser-induced fluorescence (PLIF) of formaldehyde and high-speed line-ofsight imaging of the chemically-excited hydroxyl radical (OH*). Interference of soot incandescence in experimental OH* recordings is assessed to improve interpretation of the results. Interference by poly-cyclic aromatic hydrocarbon (PAH) LIF and soot radiation is mostly evaded by evaluating flame structures shortly after ignition for one of the studied cases, but presumably included in others. Simulations were performed using a recently developed computational fluid dynamics (CFD) methodology with detailed chemistry and turbulence-chemistry interaction. Apart from the capability to model flame structures and combustion indicators based on optical diagnostics, heat-release rate trends are predicted accurately at varying boundary conditions. Significant variation in the distribution of low-temperature combustion products under heavy-duty operating conditions are explained using both CFD simulations and a one-dimensional jet model. Fuel pump Resato P16-400-2 Fuel injector Bosch CRI2 solenoid (0.205 mm) Injector driver EFS IPoD 8532 Fuel pressure sensor Kistler 4067E3000 Vessel pressure sensor Kistler 6041 AU20 Burst disk rupture pressure 35 MPa Vessel volume 1260 cc Mixing fan motor Maxon motor (custom) Inlet and exhaust valves Sitec 710.3124-D