This trial aimed to compare the success of mental-incisive nerve blocks (MINB) on mandibular premolars with symptomatic irreversible pulpitis (SIP) after oral premedication using 10 mg ketorolac or a placebo. One hundred and two patients were randomly divided into two groups. One hour prior to the administration of a MINB the patients were administered oral premedication's of either ketorolac or dextrose (placebo). The success of anaesthesia was verified by the absence of pain during the access cavity preparation or root canal instrumentation. Descriptive analysis was performed and one-way ANOVA was utilised for quantitative variables. Categorical data were analysed using chi-squared tests. Binary logistic regression was performed to assess the relationship among age, sex, type of premedication taken, preoperative pain score and tooth length to the pain outcome. The efficacy of MINB on mandibular premolars with SIP was not influenced significantly by the preoperative oral administration of ketorolac. Trial Registration: CTRI/2021/11/038115.