Multiple injection strategies are commonly used in conventional Diesel engines due to the flexibility for optimizing heat-release timing with a consequent improvement in fuel economy and engine-out emissions. This is also desirable in low-temperature combustion (LTC) engines since it offers the potential to reduce unburned hydrocarbon and CO emissions. To better utilize these benefits and find optimal calibrations of split injection strategies, it is imperative that the fundamental processes of multiple injection combustion are understood and computational fluid dynamics models accurately describe the flow dynamics and combustion characteristics between different injection events. To this end, this work is dedicated to the identification of suitable methodologies to predict the multiple injection combustion process. Two different approaches: Representative Interactive Flamelet model (RIF) and Tabulated Flamelet Progress Variable (TFPV) are compared and multiple n-dodecane Spray A injections from the Engine Combustion Network are simulated using the RANS methods with both standard k − ε and k − ω SST models. Evaluations of different turbulence and combustion models are carried out by comparing computed and measured data in terms of the mixing, penetration, first- and second-stage ignition characteristics, flame structures and soot formation.