Background: Recent trials showed improved overall survival (OS) with upfront use of docetaxel in addition to androgen deprivation therapy (ADT) in patients with hormone-sensitive prostate cancer (HSPC). We herein conducted a systemmatic review and meta-analysis to investigate the efficacy of docetaxel in different Gleason score subgroups in these trials. Methods: Randomized clinical trials (RCT) were identified after systematic searching of electronic databases (MEDLINE, PubMed, clinicaltrials.gov) and ASCO conference proceedings. Only RCT comparing ADT versus the combination of ADT plus docetaxel in patients with HSPC were included. The primary outcome measure was OS. Results were presented as hazard ratios (HR) with 95% confidence intervals (CI). We combined the HRs from each of the three trials in a meta-analysis using the random-effect model. Variation in risk ratios attributable to heterogeneity was assessed using the I-squared statistics. Results: Three eligible studies were included in this analysis (CHAARTED, GETUG-AFU-15 and STAMPEDE). STAMPEDE trial had two docetaxel arms (docetaxel+ADT and docetaxel+zolendronic acid+ADT) in comparison with ADT alone, and both arms were included as zolendronic acid had no effect on OS in this trial. Docetaxel-based chemotherapy plus ADT was associated with improved OS (HR: 0.74; 95% CI: 0.62-0.87; p < 0.001). Among patients with tumor Gleason score lower than 8, addition of docetaxel to ADT significantly improved overall survival [HR: 0.66, 95% CI: 0.52–0.85, p = 0.001]. There was a trend towards improved overall survival with docetaxel in patients with Gleason score of ≥8, although the magnitude of risk reduction was lower and did not achieve statistical significance [HR: 0.81, 95% CI: 0.64–1.02, p = 0.066]. Conclusions: This meta-analysis provides evidence that addition of docetaxel to ADT improves survival in HSPC and the benefit of docetaxel is particularly evident in patients with tumor Gleason score lower than 8. Given the OS benefit of abiraterone in the same setting, this data may be useful in tailoring treatment and in stratification of patients in comparative clinical trials of docetaxel in HSPC.