Background There is no consensus in the medical community about the prognostic role of preoperative serum levels of human epididymis protein 4 (HE4) in ovarian cancer (OC). The purpose of this meta-analysis was to establish whether preoperative serum levels of HE4 are associated with OC prognosis. Content Eligible studies were searched for in PubMed, ClinicalTrials.gov, CNKI and Wanfang Med Online. We performed a meta-analysis of 1315 OC cases from 14 published articles. Summary Our meta-analysis demonstrated that high HE4 was associated with poor overall survival (OS) (random effects model, hazard ratio [HR]=1.91, 95% confidence interval [CI]=1.40–2.614, p<0.0001; I2=52%, p=0.04) and; progression-free survival (PFS) (random effects model, HR=1.38, 95% CI=1.13–1.69, p=0.002; I2=85%, p<0.00001). However, subgroup analysis showed that high HE4 was not associated with poor OS (fixed effects model, HR=1.86, 95% CI=0.89–3.89, p=0.1; I2=34%, p=0.22) or PFS (random effects model, HR=1.34, 95% CI=0.95–1.88, p=0.1; I2=69%, p=0.007) for studies including only Asian populations. Outlook In conclusion, this meta-analysis shows that high HE4 was associated with poor OC OS and PFS overall. However, the association of high HE4 with poor OS and PFS was not observed for Asians. Large-scale, multi-center investigations should be performed.