To determine the effect of administration of pre-operative lornoxicam (LNX) or diclofenac potassium (DP) on the success of inferior alveolar nerve blocks (IANB) in patients with irreversible pulpitis in a double-blind randomised controlled trial. One hundred and fourteen patients with irreversible pulpitis of a mandibular posterior tooth participated. Patients indicated their pain scores on a Heft Parker visual analogue scale, after which they were randomly divided into three groups (n = 38). The subjects received identical capsules containing 8 mg LNX, 50 mg DP or cellulose powder (placebo, PLAC), 1 h before administration of IANB with 2% lidocaine containing 1 : 200 000 epinephrine. Lip numbness was assessed after 15 min, following which the teeth were tested with cold spray and their responses (negative or positive) were recorded. Access cavities were then prepared and success of IANB was defined as the absence of pain during access preparation and root canal instrumentation. The data were analysed using chi-squared tests. The percentages of teeth giving a negative response to cold test were 42.8% (PLAC), 78.5% (LNX) and 67.8% (DP), with no significant differences amongst the groups (P > 0.05). The success rates for the IANB in descending order were 71.4% (LNX), 53.5% (DP) and 28.5 (PLAC). A significant (P < 0.001) difference was found between the LNX and the PLAC groups only. Pre-operative administration of LNX significantly improved the efficacy of IANB in patients with irreversible pulpitis, whilst the effect of pre-medication with DP was not significantly different from the PLAC.