In the present study, trimodal high-density polyethylene (tri-HDPE) slurry phase samples from the polymerization reactors were subjected to high temperature gel permeation chromatography/size exclusion chromatography (HT-GPC/SEC) analysis. The molecular weight (Mw) and its distributions were evaluated using commercially available HT-GPC instruments equipped with different detection modes (DRI, IR5 MCT, and light scattering). The SEC studies reveal the fact that there is a considerable challenge in generating a repeatable and reproducible data for the reactor grade HDPE samples which could be attributed to different detection modes employed and instability of HDPE reactor grades which are susceptible to undergo thermo-oxidative degradation during HT-GPC analysis. Among various instrumentation and detection modes investigated, the HT-GPC with IR5 MCT detection showed reliable results (%Error <15) when compared with absolute Mw data obtained from MALS detection. Based on the findings, proposed suitable SEC mode to characterize the HDPE reactor grade polymer samples.