Aim: To determine whether photobiomodulation (PBM) therapy could increase the depth of analgesia during endodontic therapy of teeth affected with symptomatic irreversible pulpitis. Materials and methods: Forty-nine patients with symptomatic irreversible pulpitis were randomized into two groups. In the laser group, before administering anesthesia, the lower molars’ crowns were continuously treated with a diode laser (980 nm) for 20 s with a low-level laser tip in the buccal aspect close to the gingival margin. While the teeth of the second group who was blinded to the type of treatment received placebo treatment wherein the laser device was switched off. The visual analogue scale (VAS) was used to assess pain in both groups before the endodontic procedure, during dentin cutting, and at dropping pulp, wherein, the success was defined as no or mild pain. The Chi-square and independent sample t-tests were used to assess the data. Results: During dentin cutting and pulp dropping, the group receiving the laser therapy presented with less mean pain score than the placebo group which was statistically significant. Additionally, it was observed that the need for supplementary injection was less frequent in the laser-treated group than in the placebo group (p = 0.01). Conclusion: The irradiation by diode laser (980 nm) prior to administration of local anesthesia appears to be useful in minimizing discomfort and additional injection during root canal therapy (RCT). Clinical Significance: Pain management is essential for providing the best possible treatment to patients before, during, and after endodontic therapy. Adequate pain control during treatment also aids in reducing postoperative discomfort. This implies the need for additional methods to reduce discomfort during endodontic treatment; hence, adjuncts are crucial to achieving this goal. Photobiomodulation may be used as an adjuvant to reduce discomfort and supplementary injections during RCT.