Biogas is a renewable energy fuel (which can also be upgraded to biomethane), and it has the potential to substitute fossil fuels. In the present study, the effect of various biogas compositions on cycle-to-cycle variations (CCVs) of combustion is investigated while operating a spark-ignition engine at a compression ratio of 8.5:1 and engine speed of 1500 rpm. In addition, the percentage of CO2 that could be removed from a typical biogas composition (i.e., 60% CH4 and 40% CO2, by volume) as a compromise between the biogas upgrading cost and engine combustion characteristics is also determined. For a better understanding of the combustion process, a CFD model of the engine was also developed with detailed chemical kinetics, and it was validated with the experimental data. For various biogas compositions (including biomethane), carbon dioxide (CO2) percentage was varied from 0 to 40% in the fuel mixture of methane and CO2. The study showed that a linear relationship existed between peak cylinder pressure and its location, which was weakened with the increase of the CO2 percentage in the fuel mixture, and a hook-back phenomenon was observed for the case with 40% CO2 in the fuel mixture. The CCVs of indicated mean effective pressure (IMEP), flame initiation, and combustion durations were increased with the increase of the CO2 percentage in the fuel mixture. The CFD model showed that this is due to the degradation in the flame propagation process, as the concentrations of OH, H, and O radicals were found to decrease with the increase in the CO2 percentage. At a low load of 8 Nm, coefficient of variation of IMEP was increased from 3.4 to 3.6% when the CO2 percentage was increased from 0 to 20% in the fuel mixture, which, however, was significantly increased to 7.5 and 12.7% for 30 and 40% of CO2, respectively. Overall, the combustion process was significantly degraded when CO2 was more than 20% in the fuel mixture. Therefore, the removal of 20% of CO2 from a typical biogas composition provides a good compromise between the biogas upgrading cost and engine combustion characteristics. Copyright © 2019 American Chemical Society.