Background: Atrial fibrillation is the most common tachyarrhythmia, while catheter ablation is an effective therapy for atrial fibrillation. However, pain and nervousness may occur during the procedure. Moreover, a consensus has still not been reached on which is the best kind of analgesic and sedative to use in these procedures. Therefore, we conducted a network meta-analysis to evaluate the efficacy and safety of analgesics and sedatives used in catheter ablation for atrial fibrillation. Methods: We searched PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, and Baidu Wenku document download website for randomized controlled trials from their inception to February 26, 2023. Only studies that made comparisons among analgesics or sedatives and involved patients with atrial fibrillation undergoing radiofrequency catheter ablation were included. The efficacy endpoints were Ramsay sedation scores and visual analog scale scores during the radiofrequency catheter ablation for atrial fibrillation. The safety endpoints were the incidence of respiratory depression, hypotension, nausea, and vomiting. Pairwise comparisons and frequency method analyses were conducted. Results were reported as odds ratio (OR), mean difference (MD), and corresponding 95% confidence intervals (CIs). We assessed the risk bias of the studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Results: Out of the 709 articles initially retrieved, 14 studies, with a total of 1156 participants, were included. In terms of efficacy, patients receiving dexmedetomidine during radiofrequency ablation for atrial fibrillation had higher Ramsay sedation scores than those receiving midazolam plus fentanyl, or its derivatives (MD –0.88, 95% CI [–0.04 to –0.72]). Compared with morphine, dezocine (MD 1.88, 95% CI [1.16 to 2.60]), hydromorphone (MD 4.07, 95% CI [3.56 to 4.58]), butorphanol (MD 3.18, 95% CI [2.38 to 3.96]), and fentanyl or its derivatives (MD 1.57, 95% CI [1.25 to 1.89]) had a better analgesic effect. In terms of safety, propofol (OR 16.46; 95% CI [1.54 to 175.95]) and midazolam plus fentanyl or its derivatives (OR 7.02; 95% CI [1.33 to 36.99]) significantly increased the incidence of respiratory depression compared with dexmedetomidine plus fentanyl or its derivatives. Dexmedetomidine plus fentanyl or its derivatives reduced the incidence of nausea and vomiting compared with fentanyl alone (OR 4.74; 95% CI [1.01 to 22.22]). Propofol was associated with a lower incidence of nausea and vomiting than hydromorphone (OR 0.01; 95% CI [0.00 to 0.59]) and fentanyl or its derivatives (OR 0.01; 95% CI [0.00 to 0.51]). There was no statistically significant difference in the incidence of hypotension between any two strategies. Conclusions: Hydromorphone and butorphanol had better analgesic effects than fentanyl or its derivates. Dexmedetomidine had better sedative effects. In terms of safety, dexmedetomidine, oxymorphone, and butorphanol were superior. It is necessary to explore the regimen that can consider both the effectiveness and safety during radiofrequency catheter ablation for atrial fibrillation (AF). The PROSPERO Registration: This study was registered with PROSPERO, number: CRD42023403661.