Background and Objectives: Symptomatic irreversible pulpitis in permanent mature teeth is a common indication for nonsurgical root canal treatment (NSRCT), but contemporary studies have reported on vital pulp therapy (VPT) applied in such teeth as a less invasive treatment. This systematic review assessed the outcomes of VPT, including partial and full pulpotomy performed with hydraulic calcium silicate cements (HCSCs) in permanent mature posterior teeth diagnosed with symptomatic irreversible pulpitis. Materials and Methods: The PRISMA guidelines were followed. The search strategy included PubMed ®, EMBASE, Cochrane library and grey literature electronic databases. The quality assessment of the identified studies followed the Cochrane Collaboration Risk of Bias, ROBINS-I and Newcastle–Ottawa Scale tools. Results: The search of primary databases identified 142 articles, of which 9 randomized controlled trials and 3 prospective cohort studies were selected for review. The risk-of-bias was assessed as ‘high’ or ‘serious’, ‘fair’, and ‘low’ for three, seven and two articles, respectively. One to five years after VPT using HCSCs, the success rates mostly ranged from 78 to 90%. Based on two articles, the outcomes of the VPT and NSRCT were comparable at one and five years. Despite the necessity for the intra-operative pulp assessment in VPT procedures, the majority of the studies did not fully report on this step or on the time needed to achieve hemostasis. Small sample sizes, of under 23 teeth, were reported in three studies. Conclusions: The reviewed 12 articles reported favorable outcomes of the VPT performed with HCSCs in permanent mature posterior teeth with symptomatic irreversible pulpitis, with radiographic success in the range of 81 to 90%. Two articles suggested comparable outcomes of the VPT and root canal treatment. Universal case selection and outcome criteria needs to be established for VPT when considered as an alternative to NSRCT. This evidence supports the need for further research comparing longer-term outcomes of both of the treatment modalities.