The Not-to-Exceed (NTE) protocol developed in 2004 is currently used for verification of emissions compliance during in-fleet operation. However, the NTE protocol has come under scrutiny for assessment of test activity only under specific modes of in-use operation (i.e., favorable to NOx reduction aftertreatment system), therefore resulting in a limited amount of in-use activity being utilized for evaluation of the engine's compliance. This paper presents the application of an alternative concept, i.e., Vehicle Activity-based Windowing (ABW) approach to assess in-use NOx emissions rates while segregating engine and aftertreatment dependent modes of operating conditions. To this aim, in-use gaseous emissions were measured using a portable emissions measurement system (PEMS) from four modern heavy-duty (HD) trucks that were operated along four distinctive routes in Southern California. All the four trucks were equipped with diesel-fueled engines certified to the United States Environmental Protection Agency (U.S. EPA) 2010 emissions standards and were equipped with a diesel oxidation catalyst (DOC), diesel particulate filter (DPF), and selective catalytic reduction (SCR) aftertreatment configuration. Results of the study indicate that the ABW approach provides a unique opportunity of utilizing more than 90% of test activity acquired from valid ABW trips while demonstrating a characteristic comparison of NOx emissions levels from low versus medium/high power engine operation that are within as well as outside the bounds of efficient SCR operating conditions.