The prospect of analysis-driven precalibration of a modern diesel engine is extremely valuable in order to significantly reduce hardware investments and accelerate engine designs compliant with stricter fuel economy regulations. Advanced modeling tools, such as CFD, are often used with the goal of streamlining significant portions of the calibration process. The success of the methodology largely relies on the accuracy of analytical predictions, especially engine-out emissions. However, the effectiveness of CFD simulation tools for in-cylinder engine combustion is often compromised by the complexity, accuracy, and computational overhead of detailed chemical kinetics necessary for combustion calculations. The standard approach has been to use skeletal kinetic mechanisms (∼50 species), which consume acceptable computational time but with degraded accuracy. In this work, a comprehensive demonstration and validation of the analytical precalibration process is presented for a passenger car diesel engine using CFD simulations and a graphical processing unit (GPU)-based chemical kinetics solver (Zero-RK, developed at Lawrence Livermore National Laboratory, Livermore, CA) on high performance computing resources to enable the use of detailed kinetic mechanisms. Diesel engine combustion computations have been conducted over 600 operating points spanning in-vehicle speed-load map, using massively parallel ensemble simulation sets on the Titan supercomputer located at the Oak Ridge Leadership Computing Facility. The results with different mesh resolutions have been analyzed to compare differences in combustion and emissions (NOx, carbon monoxide CO, unburned hydrocarbons (UHC), and smoke) with actual engine measurements. The results show improved agreement in combustion and NOx predictions with a large n-heptane mechanism consisting of 144 species and 900 reactions with refined mesh resolution; however, agreement in CO, UHC, and smoke remains a challenge.