Fuels that can be produced in a sustainable manner are of high interest because they can provide an essential step toward net zero emissions vehicles. This study examines the combustion of one such fuel, Dimethyl Ether (DME), in a compression ignition, 4-cylinder, 2.2L engine. Testing was conducted using the Federal Test Procedure (FTP) certification cycle from the US Environmental Protection Agency (EPA). Different sets of calibration maps were designed to target low-NOx (30-50ppm) by using high EGR and intake throttle and high-NOx (approximately 1000ppm) using no EGR. An intermediate, mid-NOx calibration was also evaluated. Varying calibration approaches yielded total integrated engine out emissions ranging from 118 to 145gCO2/km, all below the 191gCO2/km from the baseline diesel. The corresponding NOx+UHC and CO emissions were also evaluated. The mid-NOx calibration was overall more favorable, as it met TIER 3-Bin 20 emissions requirements with the current efficiencies of the base engine diesel aftertreatment system. This paper reviews the transient behavior with three different calibrations, noting the effect of air-to-fuel ratios where the engine combustion efficiency deteriorates. It also highlights the impact of improved air and fuel controls, and the application of real time combustion feedback to enhance the combustion stability of the engine and the reduction of CO2 emissions. The paper explores the impact of renewable DME, and its carbon index, on the CO2 emissions for the low-NOx calibration. While a 5% renewable DME content can reduce the CO2 to the target level, the fuel consumption remains high due to the poor combustion efficiency and corresponding high HC and CO during transient operation.