A heavy-duty engine is homologated in a test cell. However, starting with Euro VI regulation, the in-service conformity is controlled with the engine installed in the vehicle using portable emission measurement systems (PEMS). In Europe, the application of solid particle number (SPN) PEMS started in 2021 for compression ignition (diesel) vehicles and in 2023 for positive ignition vehicles, thus including those operating with compressed natural gas (CNG). Even though today only particles with sizes > 23 nm are regulated, the Euro 7 proposal includes particles > 10 nm. There are not many studies on the accuracy of the SPN PEMS, especially for heavy-duty applications. In this study, PEMS measuring > 23 and >10 nm from two instrument manufacturers were compared with laboratory-grade instruments. The particle detector of one PEMS was a condensation particle counter (CPC), and of the other a the diffusion charger (DC). The results showed the robustness and good accuracy (40% or 1 × 1011 #/kWh) of the PEMS for ambient temperatures from −7 °C to 35 °C, active regeneration events, different fuels (Diesel B7, HVO, and CNG), different test cycles, cold start or hot engine operations, and high exhaust gas humidity content. Nevertheless, for the DC-based PEMS, sensitivity to pre-charged urea particles was identified, and for the CPC-based PEMS, sensitivity to pressure changes with one vehicle was nnoticed. Nevertheless, the results of this study confirm that the PEMS are accurate enough to measure even the stricter Euro 7 limits.