Mineral Trioxide Aggregate (MTA) is the gold standard for vital pulp treatment (VPT), but its superiority over novel calcium silicate-based cements in permanent teeth lacks systematic evidence. This study aimed to compare the efficacy of these materials in VPT through a network meta-analysis. A systematic search was conducted in MEDLINE, EMBASE, Cochrane Library, and Web of Science until January 20, 2024. The inclusion criteria were randomized controlled trials involving VPT with biomaterials and reversible or irreversible pulpitis diagnoses in mature permanent teeth. The primary outcome was the odds ratio (OR) of failure rates with 95% confidence intervals. In the 21 eligible trials, failure rates were significantly higher with calcium-hydroxide than MTA at six (OR 2.26 [1.52-3.36]), 12 (OR 2.53 [1.76-3.62]), and 24 months (OR 2.46 [1.60-3.79]). Failure rates for Totalfill at six (OR 1.19 [0.55-2.58]) and 12 months (OR 1.43 [0.71-2.92]), and Biodentine at six (OR 1.09 [0.66-1.78]), 12 (OR 1.21 [0.74-1.96]), and 24 months (OR 1.47 [0.81-2.68]) were not significantly different from MTA. The results were similar in the direct pulp capping subgroup, whereas, in the partial and full pulpotomy subgroup, there was not enough evidence to achieve significant differences. MTA, Biodentine, and Totalfill are the most efficient materials for VPT. However, calcium-hydroxide-based materials are not recommended in VPT.