Polyoxymethylene dimethyl ethers (OME) are promising candidates as substitutes for fossil diesel fuel. A regenerative electricity-based production, using captured airborne carbon dioxide (CO2) and hydrogen (H2) from water electrolysis as reactants, provides a valuable contribution to the energy transition in mobile applications. Besides the possibility of carbon-neutral production, OME offer the advantage of a sootless combustion, which resolves the trade-off between soot and nitrogen oxides (NOx) emissions, and supports the efforts of air pollution control. While the emission behaviour of OME-powered diesel engines in raw exhaust has been studied extensively, interactions between this exhaust and components of the after-treatment system are mainly unknown. This study contains investigations conducted using a urea dosing variation (alpha titration) on a heavy-duty engine in combination with a system for selective catalytic reduction (SCR). These investigations showed a lower NOx reduction efficiency in OME operation in partial load operation compared with the one in fossil diesel operation. This can be attributed, among other reasons, to lower exhaust temperatures in OME operation. However, the high tolerance of OME to exhaust gas recirculation (EGR) compensates for this disadvantage because of the reduction of the raw NOx emission level. The difference in SCR efficiency disappeared at a high load operation point. Additionally, the alpha titration revealed, that urea dosing decreases formaldehyde emission in the SCR system. A pre-conditioned WHSC and WHTC cycle demonstrated the potential of an OME engine with after-treatment in the form of a twin-dosing SCR system for ultra-low emissions. For the specific evaluation of the emissions during these test cycles, this study contains the detailed calculation of the required factors – so-called ‘ u-values’– for OME exhaust according to the technical standard UN/ECE R49.