Natural gas offers the potential to reduce greenhouse gas emissions from heavy-duty on-road transportation. One of the challenges facing natural gas as a fuel is that its composition can vary significantly between different fuel suppliers and geographical regions. In this work, the impact of fuel composition variations on a heavy-duty, direct injection of natural gas engine with diesel pilot ignition is evaluated. This combustion process results in a predominantly non-premixed gaseous fuel combustion event; as a result, end-gas autoignition (knock) is not a concern. Changes in the fuel composition do still impact the combustion, both through the changes in the chemical kinetics of the reactions and due to changes in the density of the fuel. Increasing concentrations of heavier hydrocarbons, such as ethane or propane, in the fuel lead to higher fuel densities and hence greater fuel mass being injected for a given injection duration. This results in a combustion that has similar peak heat-release rates but longer combustion duration. There is little impact on peak cylinder pressures or the timing of the start of the combustion. The main effect on engine emissions is a substantial increase in PM emissions, due to the greater concentrations of C2-and higher species in the fuel. Various on-board sensors can be used to monitor the engine and correct fueling to avoid engine damage. In this work, a sensing system including bearing-cap mounted accelerometers is used to detect changes in the combustion event and adjust the fueling as needed to maintain engine torque over significant fuel composition variations. These results demonstrate a potential technique for engine protection and control that can accommodate wide variations in natural gas composition.