Angiopoietin-like protein 3 (ANGPTL3) plays an important role in angiogenesis. This study aimed to examine the protein expression of ANGPTL3, and to evaluate its clinical significance in esophageal cancer. ANGPTL3 expression was detected using immunohistochemistry in 98 pairs of esophageal cancer and adjacent non-cancerous tissues. The expression levels of ANGPTL3 in esophageal cancer tissues were significantly higher than those in adjacent noncancerous tissues (P 0.05). Although ANGPTL3-negative patients had longer survival time than ANGPTL3-positive patients, the difference did not reach statistical significance (P = 0.090). Stratified analysis of ANGPTL3 expression according to clinical features revealed that there was significant association between ANGPTL3 expression and overall survival among patients aged 65 years or younger, female, or with lymph node metastasis (P < 0.05). When after adjusted for clinical features, the association remained significant only in patients aged 65 years or younger (P = 0.021).Taken together, our findings provide preliminary evidence of association of ANGPTL3 expression with the prognosis of subgroups of patients with esophageal cancer.