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IMPORTANCE: Risk of opioid use disorder, overdose, and death from prescription opioids increases as dosage, duration, and use of extended-release and long-acting formulations increase. States are well suited to respond to the opioid crisis through legislation, regulations, enforcement, surveillance, and other interventions. OBJECTIVE: To estimate temporal trends and geographic variations in 6 key opioid prescribing measures in 50 US states and the District of Columbia. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional analysis of opioid prescriptions filled nationwide at US retail pharmacies between January 1, 2006, and December 31, 2017. Data were obtained from the IQVIA Xponent database. All US residents who had an opioid prescription filled at a US retail pharmacy were included. MAIN OUTCOMES AND MEASURES: Primary outcomes were annual amount of opioids prescribed in morphine milligram equivalents (MME) per person; mean duration per prescription in days; and 4 separate prescribing rates—for prescriptions 3 or fewer days, those 30 days or longer, those with a high daily dosage (≥90 MME), and those with extended-release and long-acting formulations. RESULTS: Between 2006 and 2017, an estimated 233.7 million opioid prescriptions were filled in retail pharmacies in the United States each year. For all states combined, 4 measures decreased: (1) mean (SD) amount of opioids prescribed (mean [SD] decrease, 12.8% [12.6%]) from 628.4 (178.0) to 543.4 (158.6) MME per person, a statistically significant decrease in 23 states; (2) high daily dosage (mean [SD] decrease, 53.1% [13.6%]) from 12.3 (3.4) to 5.6 (1.7) per 100 persons, a statistically significant decrease in 49 states; (3) short-term (≤3 days) duration (mean [SD] decrease, 43.1% [9.4%]) from 18.0 (5.4) to 10.0 (2.5) per 100 persons, a statistically significant decrease in 48 states; and (4) extended-release and long-acting formulations (mean [SD] decrease, 14.7% [13.7%]) from 7.2 (1.9) to 6.0 (1.7) per 100 persons, a statistically significant ...