Objective To evaluate the effectiveness and safety of a computer-controlled periodontal ligament (PDL) injection system to the local soft tissues as the primary technique in endodontic access to mandibular posterior teeth in patients with irreversible pulpitis. Methods A total of 162 Chinese patients who had been diagnosed with irreversible pulpitis in their mandibular posterior teeth without acute infection or inflammation in the periodontal tissues were enrolled in this clinical study. The patients were divided into 3 groups according to the position of the involved tooth:the premolar group (PM, n=38), first molar group (FM, n=66), and second molar group (SM, n=58). All the patients received computer-controlled PDL injection with 4%articaine and 1∶100 000 epinephrine. Immediately after the injection, endodontic access was performed, and the degree of pain during the treatment was evaluated by the patients using Visual Analogue Scale for pain. The success rates were compared among the 3 groups. The responses of local soft tissues were evaluated 3-8 days and 3 weeks after the procedure. Results The overall success rate was 76.5%. There was a significant difference in success rates among the PM, FM, and SM groups (92.1%, 53.0%, 93.1%, respectively;χ2=34.3, P