AbstractBackgroundA high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha₂ adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed.AimTo investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery.MethodsTwo separate randomised, blinded, placebo‐controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 μg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 μg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05.OutcomesThe primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered.ConclusionThis study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.