Heavy-duty vehicles require expensive aftertreatment systems for control of emissions such as particulate matter (PM) and nitrogen oxides (NOx) to comply with stringent emission standards. Reduced engine-out emissions could potentially alleviate the emission control burden, and thus bring about reductions in the cost associated with aftertreatment systems, which translates into savings in vehicle ownership. This study evaluates potential reductions in manufacturing and operating costs of redesigned emission aftertreatment systems of line-haul heavy-duty diesel vehicles (HDDVs) with reduced engine-out emissions brought about by co-optimized fuel and engine technologies. Three emissions reduction cases representing conservative, medium, and optimistic engine-out emission reduction benefits are analyzed, compared to a reference case: the total costs of aftertreatment systems (TCA) of the three cases are reduced to $11,400(1.63 ¢/km), $9,100 (1.30 ¢/km), and $8,800 (1.26 ¢/km), respectively, compared to $12,000 (1.71 ¢/km) for the reference case. The largest potential reductions result from reduced diesel exhaust fluid (DEF) usage due to lower NOx emissions. Downsizing aftertreatment devices is not likely, because the sizes of devices are dependent on not only engine-out emissions, but also other factors such as engine displacement. Sensitivity analysis indicates that the price and usage of DEF have the largest impacts on TCA reduction.