With increasingly stringent emissions regulations, the use of pre-chamber combustion systems is gaining popularity in Internal Combustion Engines (ICE). The advantages of pre-chambers are well established, such as improving fuel economy by increasing the lean limit and reducing emissions, particularly NOX. In pre-chamber combustion, flame jets shoot out from the pre-chamber orifices into the main chamber, generating several ignition points that promote a rapid burn rate of the lean mixture (excess-air ratio (λ) >1) in the main chamber. This work studies the effects of using two different fuels in the main chamber and assesses the lean limit, the combustion efficiency (ηc), and the emissions of a single-cylinder heavy-duty engine equipped with a narrow-throat active pre-chamber. Ethanol (C2H5OH) was tested in the main chamber while keeping the pre-chamber fueled with methane (CH4), and the results were then compared to using methane as the sole fuel. The engine was operated at a fixed speed, intake pressure, and spark-timing. The amount of fuel injected was varied to attain different global λ, and then, for each global λ, the amount of fuel injected to the pre-chamber was varied to observe the effect of the pre-chamber λ. Different air intake temperatures were tested to observe the effect on combustion efficiency. The results showed an increase in the lean limit using ethanol in the main chamber compared to using only methane in both chambers. Also, ethanol showed a lower combustion efficiency than that of methane, however ηc improved when the air intake temperature increased.