While endometrial cancer (EC) has an overall favorable prognosis, some patients do poorly and may benefit from refinements of current classification systems. Molecular classification stratifies ECs into four prognostic groups: POLEmut, MMRd (mismatch repair deficient), p53abn, and NSMP (no specific molecular profile), where POLEmut has the best prognosis and p53abn has the worst prognosis. We used proteomic profiling to provide additional prognostic or predictive information for EC patients, across or within molecular subtypes. Global proteome profiling of formalin fixed, paraffin embedded samples, that had clinicopathologic and outcome data, was performed on 184 ECs encompassing all four molecular subtypes, including replicate samples of the same tumor, and both biopsy and final hysterectomy specimens. To ensure representation of each subtype, we profiled an approximately equal distribution in the 148 unique tumors; 34 (23%) POLEmut, 40 (23%) MMRd, 35 (24%) p53abn and 39 (26%) NSMP, rather than the population-based distributions. There was high reproducibility in the proteomic profiles of intra-tumor replicate samples, and between matched biopsy and hysterectomy tumor samples. Consensus clustering identified four clusters with different prognosis, named ‘Adhesion’, ‘Immune’, ‘Proliferation’, and ‘Metabolic’ based on proteins enriched in each cluster. We correlated protein expression with common mutations, molecular subtypes, and outcomes. Proteomic analysis of EC identified candidate prognostic markers that may further refine current molecular classification and help guide treatment decisions. These data offer insights into new therapeutic interventions that could be developed to target proteins and pathways identified by EC proteomic profiling.