Anesthesia is a technique for reducing or eliminating pain, in medical and dental practice, local anesthetics have a long history of efficacy and safety. Persistent postoperative pain (PPP) is caused by tissue damage so local anesthetics used to block bundles or roots of nerves in the central nervous system is one technique to prevent persistent postoperative pain (PPP). Aim of this study aimed to synthesize outcome data across systematic review and meta-analysis for comparing local and regional anesthesia versus conventional analgesia to prevent persistent postoperative pain in adults and children undergoing surgery. Methods: Online databases Medline, Pub Med, and Google Scholar of Randomized controlled trials published between 2014 and 2021. The PRISMA checklist was utilized to guide this review.. Results: 8 RCTs studies in the review; (2) RCTs favored epidural anesthesia for thoracotomy suggesting the odds of having PPP three to 18 months following an epidural for thoracotomy, (1) RCTs favored regional anesthesia after caesarean section, (5) RCTs also favored the infusion of intravenous local anesthetics for the prevention of PPP three to six months after breast cancer surgery. The regional anesthesia may moderate reduce the risk of developing PPP after thoracotomy and caesarean section. There is low evidence that regional anesthesia may reduce the risk of developing PPP after breast cancer surgery. Conclusions: This meta-analysis found that localized anesthesia has potential benefits, such as reduced post-anesthesia care unit utilization, nausea, and postoperative pain. Keywords: regional anesthesia, local anesthesia, and persistent postoperative pain (PPP).