Polyoxymethylene dimethyl ethers (OME) are promising e-fuels for diesel engines, combining carbon-neutral production and low-emission engine operation by virtue of soot-free combustion. The emissions of diesel engines fueled with OME and in blends with diesel have been studied extensively using single-cylinder research engines under laboratory conditions. Emissions from a series engine using an exhaust after-treatment system (ATS) – especially in cold-start operation – are largely unexplored. This study presents investigations conducted using a heavy-duty engine with ATS in a transient driving cycle including cold-start operation. Measurements from a Fourier transform infrared spectrometer (FT-IR) showed that formaldehyde and formic acid form the largest proportion of the monitored tailpipe exhaust emissions due to incomplete combustion in cold-start operation, as long as the catalysts are below their light-off temperature. Non-target screening using a mass spectrometer for online characterization of both gaseous and aerosol exhaust revealed that unburned OME accounts for the majority of gaseous emissions of heavy species in raw exhaust, independent of cold- or hot-start. The ATS removes OME in the exhaust equally in the cold and the hot run. Additionally, this study presents results with specific measures taken for ATS heating such as electrical heating and fuel dosing – demonstrating that electrical heating in combination with an early start of fuel dosing reduces nitrogen oxide (NO_x) emissions in the transient driving cycle by 64.9%, but at the cost of an increase in formaldehyde emission of 58.3%. A later start of fuel dosing avoids this increase and reduces NO_x emissions by 61.8%.