We performed a systematic review and network meta-analysis (NMA) to assist clinicians in determining the optimal patient-specific method of analgesia during radial artery puncture by comparing radial artery puncture procedural pain. We included randomized controlled trials that assessed the prophylactic efficacy of local anesthesia for radial artery puncture-associated pain. We searched the Medical Literature Analysis and Retrieval System Online in January 2023, the Cochrane Central Register of Controlled Trials in January 2023, the Excerpta Medica Database in December 2022, the World Health Organization International Clinical Trials Platform Search Portal in January 2023, and ClinicalTrials.gov in January 2023. We synthesized the pain scores (0-100 scale) using the frequentist random-effects NMA model. We evaluated the confidence in each outcome using the CINeMA tool (https://cinema.ispm.unibe.ch/). We conducted an NMA of 1,619 patients across 14 studies on pain scores during radial artery puncture-related procedures for 12 interventions. Compared with placebo, mepivacaine infiltration and lidocaine spray probably reduce pain (mean difference (MD): -47.67, 95% confidence interval (CI): -61.45 to -33.89, confidence rating (CR): moderate; MD: -27.38, 95% CI: -37.53 to -17.22, CR: moderate). Of the 32 studies included, none reported systemic adverse events, such as anaphylaxis or local anesthetic systemic toxicity, or severe local adverse events. In conclusion, mepivacaine infiltration and lidocaine spray probably reduce the pain associated with radial artery puncture more than other local anesthesia.