BACKGROUND Inferior alveolar nerve block is a common technique for anesthesia of the primary mandibular molars. A number of disadvantages have been shown to be associated with this technique. Periodontal ligament (PDL) injection could be considered as an alternative to inferior alveolar nerve block. The aim of this study was to evaluate the effectiveness of PDL injection in the anesthesia of primary molar pulpotomy with mandibular block. METHODS This study was performed using a sequential double-blind randomized trial design. 80 children aged 3-7 years old who required pulpotomy in symmetrical mandibular primary molars were selected. The teeth of these children were anesthetized with periodontal injection on one side of the mandible and block on the other. Pulpotomy was performed on each patient during the same appointment. Signs of discomfort, including hand and body tension and eye movement, the verbal complaint and crying (SEM scale), were evaluated by a dental assistant who was blinded to the treatment allocation of the patients. Finally, the data were analyzed using the exact Fisher test and Pearson Chi-squared exact test. RESULTS Success rate was 88/75 and 91/25 in the PDL injection and nerve block groups, respectively. There was no statistically significant difference between the two techniques (P = 0.250). CONCLUSIONS Results showed that PDL injection can be used as an alternative to nerve block in pulpotomy of the mandibular primary molars.