Clinicians are increasingly being challenged by patients who are treated for chronic pain with high-dose opioids that can cause medical, social, and societal harm. These patients may best be improved by psychological approaches, adjuvant medications, and opioid reduction or removal, rather than ever-escalating dosing that has become common. Opioid reduction or removal can be a difficult process that, when done incorrectly, may cause patient dissatisfaction or severe discomfort. Buprenorphine, a partial opioid agonist, is slowly becoming recognized as an effective pain treatment, possessing a wide safety margin while offering the opportunity for stabilization of opioid dosing or even removal. We have developed a protocol for hospitalization of the most fragile or toxic patients detailed herein that can permit a comfortable conversion to buprenorphine from prior high-dose full agonist opioid therapy. Seventy-six consecutive patients with serious medical, psychological, or addiction comorbidities, treated with morphine equivalent doses exceeding hundreds of milligrams per day, were followed after conversion for up to 25 months. Two-thirds reported moderate to dramatic improvements of pain and functional status with an increase seen in employment. Median length of hospital stay was 2 days, and the median daily buprenorphine discharge dose was 8 mg. No adverse reactions or outcomes were observed. A brief hospitalization for conversion from high-dose opioid therapy to a safer, more effective buprenorphine regimen can produce life-altering improvement.