Regarding the comparison of cardiovascular disease risk between gonadotropin-releasing hormone (GnRH) antagonists and GnRH agonists, there are discrepancies in results from different studies. Therefore, this meta-analysis was conducted to investigate whether degarelix could reduce cardiovascular disease risk. We systematically searched the PubMed, Embase, Web of Science, and Cochrane Library databases with a search time limit of up to December 2023 for articles focusing on the use of degarelix, a GnRH antagonist, in prostate cancer, with an emphasis on articles comparing degarelix to GnRH agonists. Study endpoints included major adverse cardiovascular events, stroke, all-cause mortality, myocardial infarction, heart failure, and arrhythmia. A total of 1320 articles were retrieved, of which eight met our inclusion criteria and involved 138-065 patients. The pooled results showed no difference in the risk of major adverse cardiovascular events (hazard ratio [HR]=0.94, 95% confidence interval [CI]: 0.65-1.35; P=0.73), stroke (HR=0.89, 95% CI: 0.62-1.27; P=0.52), myocardial infarction (HR=0.98, 95% CI: 0.70-1.37; P=0.91), all-cause mortality (HR=1.09, 95% CI: 0.73-1.65; P=0.67), and arrhythmia (risk ratio=0.64, 95% CI: 0.15-2.76; P=0.55) between degarelix and GnRH agonists. However, degarelix reduced the risk of heart failure (HR=0.56, 95% CI: 0.36-0.88; P=0.01). Further clarification on the effects of different androgen deprivation therapy modalities on cardiovascular disease is needed from future and larger prospective randomized controlled trials.