The stringent emission norms over the past few years have driven the need to use low-carbon fuels and after treatment technology. Natural gas is a suitable alternative to diesel heavy-duty engines for power generation and transportation sectors. Stoichiometric combustion offers the advantages of complete combustion and low carbon dioxide emissions. Turbocharging and cooled exhaust gas recirculation (EGR) technology enhances the power density along with reduced exhaust emissions. However, there are several constraints in the operation of natural gas spark ignition engine such as exhaust gas temperature limit of 780 °C, sufficient before turbine pressure for EGR drivability, boost pressure, peak cylinder pressure limit and knocking. These limits coulld restrict the engine BMEP (brake mean effective pressure). In the present study, tests were conducted on a V12, 24 liters, heavy duty natural gas fuelled spark ignition engine (600 HP) with different EGR and turbocharger configurations to achieve 16 bar BMEP without abnormal combustion. Considering the maximum exhaust temperature limit of 780 °C of exhaust system, minimal engine hardware changes were done to ensure less complexity, cost-effective engine development with robust design. The turbine trim was decreased from 89% to 84% to avoid excessive high before turbine backpressure, backflow of residual gases into cylinder and knock possibility. EGR system optimization with mixer enhanced EGR mixing and distribution in all cylinders that improved BSFC by 3%. During knock calibration, the offset to base ignition timing was used for individual cylinders to mitigate knock. Endurance trial of 100 hours was carried out to validate the reliability of engine design and calibration, and no issues were detected. The developed engine is the highest BMEP V12 engine in its segment in India using stoichiometric combustion with cooled EGR and three-way catalyst. The engine is certified with latest Indian CPCB IV+ emissions norms.