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Aims: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. Methods: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18‐month overall survival (OS), treatment‐emergent adverse events (TEAEs), hypertension and fatigue. The network meta‐analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. Results: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). Conclusions: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC. [ABSTRACT FROM AUTHOR]