Sickle cell disease (SCD) is a hematologic disorder defined by presence of sickle-shaped red blood cells that can occlude blood vessels and cause tissue ischemia and pain. Treating SCD pain adequately and safely is difficult given today’s opioid climate. Buprenorphine-naloxone has been described as an alternative option to treat chronic pain in the adult literature, however, it historically has required discontinuation of full-agonist opioids before initiation, resulting in opioid withdrawal symptoms. Here we present two adolescents with SCD who successfully weaned off large doses of full-agonist opioids by using a micro-dose induction of buprenorphine-naloxone in clinic without patients experiencing withdrawal symptoms. Ambulatory micro-dose induction may remove hurdles that otherwise would discourage patients from trying this regimen while still controlling pain safely.