Reduced emissions, improved fuel economy, and improved performance are a priority for manufacturers of internal combustion engines. However, these three goals are normally interrelated and difficult to optimize simultaneously. Studying the experimental heat release provides a useful tool for combustion optimization. Heavy-duty diesel engines are inherently transient, even during steady state operation engine controls can vary due to exhaust gas recirculation (EGR) or aftertreatment requirements. This paper examines the heat release and the derived combustion characteristics during steady state and transient operation for a 1992 DDC series 60 engine and a 2004 Cummins ISM 370 engine. In-cylinder pressure was collected during repeat steady state SET and the heavy-duty transient FTP test cycles. The 95% confidence interval for a set of three FTP tests was used to determine significant differences in the calculated and acquired combustion parameters between cylinders, repeat tests (days and months later), fuels, engines, and a repeat section of the FTP. During the 11 repeat SET tests, the premix spike in the heat release rate proved to be the least repeatable parameter. Directly measured combustion parameters showed the lowest variation with COVs of 0.2%, 0.4%, and 0.3% for the engine speed, maximum in-cylinder pressure, and exhaust temperature, respectively. Significant differences in the heat release parameters from the transient testing occurred more frequently between cylinders, fuels, and engines than between repeat tests, although, the frequency of significant differences increased with repeat tests conducted two month later. At idle, the 1992 DDC engine showed higher variability in measured parameters than the 2004 Cummins engine due to intermittent fuel injection in each cylinder.