Background: Eastern Cooperative Oncology Group Performance Status (ECOG PS) has been shown to be a strong predictor of mortality among patients with advanced cancer. However, in metastatic prostate cancer, there has been heterogeneity in the literature regarding the strength of association between different ECOG categories and overall survival (OS). Therefore, we conducted a systematic search and meta-analysis of studies reporting on the prognostic value of ECOG PS on OS within the metastatic prostate cancer population. Methods: We performed a systematic search of the literature within the Medline (PubMed) database from inception until March 21^st 2022. Both trials and real-world data (RWD) studies were included. Using a random-effects model, a meta-analysis pooling ECOG categories on OS was performed separately for metastatic castrate resistant prostate cancer (mCRPC) and metastatic castrate sensitive prostate cancer (mCSPC) studies. We also stratified the analyses by prior use of chemotherapy and study type (RWD vs. Trial). Between-study heterogeneity was analyzed using the I² statistic. Results: A total of 75 studies met the eligibility criteria, comprising of 32,298 patients. Nearly all studies (72 out of 75) were among patients with mCRPC, while the remaining three studies were among mCSPC patients. Overall, all ECOG PS categories were associated with OS, with the highest estimate observed among mCRPC patients with ECOG PS of ≥2 vs. <2 ([HR] = 2.10; 95% confidence interval [CI]: 1.87 to 2.37). In secondary analyses, among mCRPC patients with ECOG PS of ≥1 vs. <1, there was a significant difference according to study type (RWD: HR=1.98, 95% CI: 1.73 to 2.26 vs. trials HR=1.32, 95% CI: 1.13 to 1.54). There were no significant differences in the pooled HR of OS stratified by previous chemotherapy across all three ECOG PS categories. Conclusions: Overall, ECOG PS was a significant predictor of OS regardless of category, previous chemotherapy, and type of metastatic population, although differences were observed in RWD vs. trial populations. Additional studies are needed to quantify the association between ECOG PS and OS in the mCSPC population, as well as to better understand the role of ECOG PS on outcomes in RWD vs. trials of cancer treatments.