The present study evaluates the effect of engine speed, exhaust gas recirculation (EGR), and compression ratio on conventional diesel combustion (CDC) and two isobaric combustion cases, by utilizing multiple injection strategies. The experiments were conducted in a Volvo D13C500 single-cylinder, heavy-duty engine, fuelled with standard European Union (EU) diesel fuel. The engine was operated at three different speeds of 1200, 1500, and 1800 revolutions per minute (rpm). For each engine speed and combustion cases, the EGR rate was varied from 0% to 40%. The low-pressure isobaric combustion (IsoL) and high-pressure isobaric combustion (IsoH) were maintained at peak cylinder pressure (PCP) of 50 and 68 bar, respectively, which was representative of the peak motoring pressure (PMP) and PCP of CDC. This was possible by adjusting the intake air pressure to 1.7 and 2.3 bar—absolute for IsoL and IsoH, respectively, at 1200 rpm. At a higher engine speed, the intake air pressure was further increased to maintain top dead center (TDC) pressure. Irrespective of engine speed and EGR rates, it was found that IsoH has similar or higher gross indicated efficiency than CDC with the lowest efficiency for IsoL. The heat transfer losses were lower while the exhaust losses were higher for isobaric cases, compared to CDC. The heat transfer losses were further reduced due to limited time availability at higher engine speeds with a penalty in higher exhaust losses for all combustion cases. This additional exhaust energy would not be totally lost as it can be converted into useful work using an expander cylinder of the double compression expansion engine (DCEE) concept. At a given engine speed, higher EGR rates resulted in higher carbon monoxide (CO)/unburnt hydrocarbon (UHC)/soot emissions with lower nitrogen oxides (NOx) emissions. However, with increased engine speed, CO and UHC emissions were highly unchanged. A typical soot-NOx trade-off characteristic can be seen with increased soot and reduced NOx emissions, largely due to reduced charge premixing time at higher engine speed. From the compression ratio comparison results, it was found that a lower compression ratio resulted in reduced gross indicated efficiency and increased exhaust losses. Compared to the higher compression ratio, the lower compression ratio also led to lower heat transfer losses due to reduced combustion temperature. Besides, the NOx emissions were reduced with increased soot concentration at the lower compression ratio.