Gaseous and particulate matter (PM) emissions were assessed from two current technology heavy-duty vehicles operated on CARB ultra-low sulfur diesel (ULSD), hydrotreated vegetable oil (HVO) blends, and a biodiesel blend. Testing was performed on a 2014 model year Cummins ISX15 vehicle and on a 2010 model year Cummins ISB6.7 vehicle. Both vehicles were equipped with diesel oxidation catalysts (DOC), diesel particulate filter (DPF), and selective catalytic reduction (SCR) systems. Testing was conducted over the Heavy-Duty Urban Dynamometer Driving Schedule (UDDS) and Heavy Heavy-Duty Diesel Truck (HHDDT) Transient Cycle. The results showed lower total hydrocarbons (THC), non-methane hydrocarbons (NMHC), and methane (CH4) emissions for the HVO fuels and the biodiesel blend compared to CARB ULSD. Overall, nitrogen oxide (NOx) emissions showed discordant results, with both increases and decreases for the HVO fuels. NOx emissions with the biodiesel blend for both vehicles were higher compared to the HVO fuels and CARB ULSD. Carbon dioxide (CO2) emissions were generally lower for the HVO fuels relative to CARB ULSD, but not for the biodiesel blend. Fuel economy showed some significant reductions for the HVO fuels and the biodiesel blend over both test cycles for one of the vehicles, but not for the other. PM mass emissions were higher for the biofuels, while particle number emissions were lower. Results of the particle size distribution for the ISX-15 vehicle revealed bimodal size distribution profiles for most cases, with a nucleation mode centered from 9 to11 nm size range and an accumulation mode peaking at around 125 nm.