Objectives: Inferior alveolar nerve block (IANB) is commonly used for mandibular dentoalveolar surgery. The objective of this study was to evaluate and compare the effectiveness of coadministration of dexamethasone (4 mg/mL) or adrenaline (0.01 mg/mL) as an adjuvant with lignocaine 2% in IANB during third molar surgery (TMS). Patients and Methods: This double-blind, randomized controlled trial was conducted between March and August 2020. The investigators screened patients needing elective TMS under local anesthesia. Based on strict inclusion and exclusion criteria, patients were enrolled in this study. These patients were assigned randomly into two study groups: dexamethasone group (DXN) or adrenaline group (ADN). Outcome variables were postoperative edema, trismus, visual analogue scale (VAS), perioperative analgesia, onset time, and duration of IANB. Results: Eighty-three patients were enrolled in this study, of whom 23 (27.7%) were eliminated or excluded during follow-up. This study thus included data from 60 samples. Mean age was 32.28±11.74 years, including 28 females (46.7%) in the ADN (16 patients, 57.1%) and DXN (12 patients, 42.9%) groups. The duration of action for DXN (mean±standard deviation [SD], 4:02:07±0:34:01 hours; standard error [SE], 0:06:00 hours; log-rank P=0.001) and for ADN (mean±SD, 1:58:34±0:24:52 hours; SE, 0:04:42 hours; log-rank P=0.001) were found. Similarly, time at which 1st analgesic consume and total number of nonsteroidal antiinflammatory drugs need to rescue postoperative analgesia was found statistically significant between study groups (t (58)=–11.95; confidence interval, –2:25:41 to –1:43:53; P=0.001). Early-hours VAS was also significantly different between the study groups. Conclusion A single injection of dexamethasone prolongs the duration of action of lignocaine 2% IANB. Additionally, it can be used in cases where adrenaline is contraindicated.