Summary Objectives To evaluate the effects of minimally invasive micro-osteoperforations (MOPs) on orthodontic tooth movement and pain. Design Prospective, split-mouth, randomized controlled trial. Setting Single-centre, university hospital. Methods Twenty subjects requiring maxillary first premolar extractions were included. Right and left sides of the maxilla were randomly allocated into experimental and controls. Space closure was initiated following alignment on 0.20″ stainless steel archwires, using 150 g force, applied by coil springs on power arms. Nance-TPA was used for anchorage. On the experimental side, two 5 mm deep MOPs in vertical alignment on distal aspect of the maxillary canine mid-root region were performed prior to space closure. Outcomes The primary outcome was the amount of tooth movement during space closure, measured every 4 weeks for 12 weeks (T1, T2, and T3). Secondary outcome was the pain levels related to MOP, measured using Visual Analogue Scale (VAS) questionnaires. Significance was set at P < 0.01. Randomization Randomization was generated using a randomization table, and allocation was concealed in sequentially numbered, opaque, sealed envelopes. Blinding Blinding was not possible during the experiment but assessor was blinded during outcome assessment. Results All subjects completed the study, with tooth movement measurements available for all 20 patients for T0–T2. In three patients, space was closed on one side at T2. The average tooth movement between sides at three intervals (T0–T1, T1–T2, and T2–T3) were not significantly different. Overall difference following 12 weeks (T0–T3) was 0.69 mm higher on the experimental side (P < 0.001). No harms were observed. Limitations Short-term study, cast measurements done with digital callipers. Conclusion This 12-week randomized split-mouth controlled clinical trial showed two MOPs that are 5 mm deep, applied once prior to space closure, did not create clinically significant increase in maxillary premolar space closure. Protocol The protocol was not published before trial commencement. Registration Trial was not registered. Funding The Australian Society of Orthodontists Foundation for Research and Education.