AIM: To investigate the relationship between the levels of prostaglandin E2 (PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs. METHODS: Tear samples were collected from 36 non-Sjögren syndrome dry eye patients (10 males and 26 females, mean age 50.11±11.17y). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time (TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay (ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction (MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores (R=0.608, P<0.001), however, they did not significantly associate with TBUT (R=0.153, P=0.373), Schirmer scores (R=-0.098, P=0.570), ocular surface staining scores (R=0.282, P=0.095), and stage of MGD (R=-0.107, P=0.535). Male sex was significantly negatively correlated with tear PGE2 levels. CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.