Since early 2010, most new medium- and heavy-duty diesel vehicles in the US rely on urea-based Selective Catalytic Reduction (SCR) technology for meeting the most stringent regulations on nitrogen oxides (NOx) emissions in the world today. Catalyst technologies of choice include Copper (Cu)- and Iron (Fe)-based SCR. In this work, the performances of Fe-SCR and Cu-SCR were investigated in the most commonly used DOC + CSF + SCR system configuration. Cu-SCR offered advantages over Fe-SCR in terms of low temperature conversion, NO₂:NOx ratio tolerance and NH₃ slip, while Fe-SCR demonstrated superior performance under optimized NO₂:NOx ratio and at higher temperatures. The Cu-SCR catalyst displayed less tolerance to sulfur (S) exposure. Reactor testing has shown that Cu-SCR catalysts deactivate at low temperature when poisoned by sulfur. The impact of sulfur on the Cu-SCR system was studied by exposing the catalysts to 350 ppm S fuel and measuring the system performance during engine transient and steady state conditions. Results revealed that, despite the negative impact that sulfur can have on Cu catalysts, practical standard operation modes and current system regeneration strategies sufficed to maintain the high NOx conversion performance required for the system. In this work, the performance of Cu- and Fe-SCR in the DOC + CSF + SCR configuration was also tested on field vehicles. Consistently high NOx conversion was observed during months of field trials on low temperature applications.