Background: While reduced exposure to prescription opioids may decrease risks, including overdose and opioid use disorder, abrupt tapering or discontinuation may pose new risks. Objectives: To examine potentially unsafe tapering and discontinuation among dosage changes in opioid prescriptions dispensed to US patients on high-dose long-term opioid therapy. Design: Longitudinal observational study of adults (>18 years) on stable high-dose (>50 oral morphine milligram equivalents [MME] daily dosage) long-term opioid therapy during a 180-day baseline and a 360-day follow-up using all-payer pharmaceutical claims data, 2017-2019. Measures: Dosage tapering, increases, and/or stability during follow-up; sustained dosage stability, reductions, or discontinuation at the end of follow-up; and tapering rate. Patients could experience more than one outcome during follow-up. Results: Among 595,078 patients receiving high-dose long-term opioid therapy in the sample, 26.7% experienced sustained dosage reductions and 9.3% experienced discontinuation. Among patients experiencing tapering, 62.0% experienced maximum taper rates between > 10-40% reductions per month and 36.1% experienced monthly rates > 40%. Among patients with mean baseline daily dosages > 150 MME, 47.7% experienced a maximum taper rate > 40% per month. Relative to baseline, 19.7% of patients experiencing tapering had longterm dosage reductions > 40% per month at the end of follow-up. Implications: Dosage changes for patients on high-dose long-term opioid therapy may warrant special attention, particularly over shorter intervals, to understand how potentially sudden tapering and discontinuation can be reduced while emphasizing patient safety and shared decision-making. Rapid discontinuation of opioids can increase risk of adverse outcomes including opioid withdrawal.