Whilst the role of eukaryotic translation initiation factors (eIFs) has already been investigated in several human cancers, their role in endometrial cancer (EC) is relatively unknown. In the present retrospective study, 279 patients with EC (1180 samples) were included (mean age: 63.0 years, mean follow-up: 6.1 years). Samples were analysed for expression of 7 eIFs subunits (eIF2α, eIF3c, eIF3h, eIF4e, eIF4g, eIF5, eIF6) through immunohistochemistry and western blotting. Fifteen samples of healthy endometrium served as controls. Density and intensity were assessed and mean combined scores (CS) calculated for each patient. Upon immunohistochemistry, median eIF5 CS were significantly higher in EC as compared with non-neoplastic tissue (NNT, < 0.001), whilst median eIF6 CS were significantly lower in EC ( < 0.001). Moreover, eIF5 ( = 0.002), eIF6 ( = 0.032) and eIF4g CS ( = 0.014) were significantly different when comparing NNT with EC grading types. Median eIF4g CS was higher in type II EC ( = 0.034). Upon western blot analysis, eIF4g ( < 0.001), peIF2α ( < 0.001) and eIF3h ( < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT ( < 0.001). The remaining eIFs were non-significant. Besides tumour stage ( < 0.001) and patient's age ( < 0.001), high eIF4g CS-levels were independently associated with poor prognosis (HR: 1.604, 95%CI: 1.037-2.483, = 0.034). The other eIFs had no prognostic significance. Notably, the independent prognostic significance of eIF4g was lost when adding tumour type. Considering the difficulties in differentiating EC type I and II, eIF4g may serve as a novel prognostic marker indicating patient outcome.