Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease from full agonist opioids to buprenorphine using a method developed in the past ten years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high-dose chronic opioid therapy with inadequate response; often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are post-induction adverse events. There were seven adverse events in the first three days following standard induction, two of which were judged to be definitely related to the induction but none with any lasting sequelae. At six months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the six months pre-induction to 2.89 (SD 3.40) in the six months post induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to chronic opioid therapy with early evidence of benefit for high utilizing patients with SCD. This article is protected by copyright. All rights reserved.