Aim: The study aimed to assess pain levels after repeated platelet-rich fibrin injections (i-PRF) on both buccal and palatal alveolar sides or without any injections during orthodontic maxillary canine retraction. Methods: This trial design was a split-mouth randomized clinical trial included 18 patients with 36 maxillary quadrants randomly divided into three groups. Intervention sides received either two-time or four-time platelet-rich fibrin injections, while the control sides received no injections before starting the canine retraction phase. The enrolled patients required 1st premolar extractions in both sides followed by canine retraction. Canines were retracted using a NiTi closed spring that delivered 150 mg force stretched between hooks on canine’s bracket and mini-screw as temporary anchorage device. The i-PRF was obtained from 20 ml of blood drawn from the patient’s brachial vein and centrifuged at 700rpm for 3 minutes. Approximately 3 mL of i-PRF was injected submucosally into buccal and palatal sides midway between canine and second premolar teeth. Pain assessment was carried out using a questionnaire with a 100 mm visual analog scale to determine the pain level at 24 hours, 48 hours, and 72 hours after the injection. The Wilcoxon signed rank test was used to compare pain levels between two sides, while Friedman’s test detected changes over time. Results: There were no statistically significant differences in pain levels between the groups at each time point (P > 0.05). Besides, pain levels were significantly reduced over time in each group. Conclusions: Using both protocols of i-PRF, either two-time or four-time injections during maxillary canine retraction procedures did not considerably affect pain levels. Moreover, repeated application of i-PRF did not substantially affect pain perception.