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 is described in adult literature where it typically requires withdrawal of full-agonist opioids and inpatient hospitalization. Here we present two adolescents with SCD who successfully weaned off large doses of full-agonist opioids by using micro-dose induction of buprenorphine-naloxone in clinic. Ambulatory micro-dose induction may remove hurdles that otherwise would discourage patients from trying this regimen while still controlling pain safely.