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Introduction: The most important aspect of endodontic treatment is pain control. The quest for newer ways of pain control is always a topic of interest among the researchers. Though local anaesthesia proved to be the effective method of pain control, there are many instances of failure to achieve successful anaesthesia even with proper technique of administration in cases of irreversible pulpitis. Aim: To determine the effect of Preoperative Oral Administration of Paracetamol (PARA), Ibuprofen (IBUP) or Diclofenac Sodium (DS) on the success of maxillary infiltration anaesthesia in patients with irreversible pulpitis in a double-blinded randomised controlled trial. Materials and Methods: One hundred and twenty patients having irreversible pulpitis of a maxillary first molar were selected for this prospective, randomised, double-blind, placebo-controlled study. Patients indicated their pain scores on a Heft Parker visual analog scale, after which they were randomly divided into four groups (n=30). The subjects received identical capsules containing either 500 mg PARA, 400 mg IBUP, 50 mg DS or 400 mg lactose powder (placebo, PLAC), 1 hour before administration of maxillary infiltration anaesthesia with 2% lidocaine containing 1:80,000 epinephrine. Access cavities were then prepared and anaesthesia was defined as successful if pain is absent or patient has mild pain during access preparation and pulp extirpation. The data was analysed using two-way ANOVA and Tukey’s multiple post-hoc tests. p-value at |