Objective To compare the painless effect of four anesthetic methods during opening pulp cavity and undergoing pulpectomy for acute or chronic pulpitis. Methods 80 teeth of 80 patients were randomly allocated into four groups. Each group had 20 teeth. Anesthetic methods applied four different groups included block anesthesia of nerve, supraperiosteal infiltration, periodontal membrane injection and intrapulpal injection. Anesthesia doses were recorded and the pierced points, the zones of pain, the time of anesthesia action, the time of anesthesia persistence and the degrees of anesthesia were evaluated with four levels synthetic evaluation standard of anesthesia. Results Compared with periodontal membrane injection and intrapulpal injection, block anesthesia of nerve and supraperiosteal infiltration had the later time of anesthesia action and the longer time of anesthesia persistence(P<0.05). In four anesthetic methods, block anesthesia of nerve had the best painless effect(P<0.05). Conclusion Four anesthetic methods have their own superiorities, and we should select proper anesthetic methods in clinical work.