Published studies have investigated the prognostic role of cyclooxygenase-2 (COX-2) expression in patients with esophageal cancer (EC), but the result remains controversial. Thus, this meta-analysis was conducted to comprehensively evaluate the impact of COX-2 expression on the prognostic value in patients with EC. Relevant studies were identified from PubMed, EMBASE, and Web of Science databases. Studies that detected the COX-2 expression by immunohistochemistry and evaluated the relationship between COX-2 expression and overall survival (OS) or clinicopathological parameters were used in our analysis. The summary hazard ratios (HRs) or odds ratios were calculated to assess the risk or hazard association. A total of 25 studies, which included 2,465 patients, were included in our meta-analysis. Our analysis suggested that overexpression of COX-2 was associated with poor OS (HR =1.60, 95% CI =1.32–1.94, P<0.001). Subgroup analyses by race, percentage of high/positive COX-2 expression, histology type, treatment, and sample size all suggested significant association. Moreover, overexpression of COX-2 was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. This meta-analysis suggested that overexpression of COX-2 might serve as a prognostic biomarker for EC. Large well-designed prospective studies are needed to confirm our conclusion.