BACKGROUND AND PURPOSE: Published data on the relationship of hormone replacement therapy (HRT) with Parkinson's disease (PD) were inconclusive. Thus, a systematic meta-analysis of observational studies was performed to clarify this topic. METHODS: The databases of PubMed and EMBASE were searched for case-control or cohort studies published up till June 2, 2014. Meta-analysis of the relative risks (RRs) with 95% confidence intervals (CIs) was estimated using random-effects models. RESULTS: A final total of ten case-control and four cohort studies were included in our meta-analysis. The overall combined RR of PD for ever users versus never users of HRT was 1.00 (95% CI: 0.84-1.20). Limited to those subjects who only use estrogen, a similar trend was detected (RR: 0.95, 95% CI: 0.69-1.30). In the subgroup analysis by study design, no significant association was observed in case-control studies (RR: 0.79, 95% CI: 0.62-1.02), whereas a positive association was found in cohort studies (RR: 1.24, 95% CI: 1.10-1.40). In further analysis according to study quality, an inverse association was found in the low-quality group (RR: 0.58, 95% CI: 0.40-0.82), whereas a positive association was found in the high-quality group (RR: 1.16, 95% CI: 1.02-1.31). CONCLUSION: In summary, our results of meta-analysis do not support a protective role of HRT in female PD development.