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Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2017 in nonfederal hospitals, clinics, and overall (all sectors).Drug expenditure data through calendar year 2016 were obtained from the QuintilesIMS National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2017, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2017 for nonfederal hospitals, clinics, and overall (all sectors) were made based on a combination of quantitative analyses and expert opinion.Total U.S. prescription sales in the 2016 calendar year were $448.2 billion, a 5.8% increase compared with 2015. More than half of the increase resulted from price hikes of existing drugs. Adalimumab was the top drug overall in 2016 expenditures ($13.6 billion); in clinics and nonfederal hospitals, infliximab was the top drug. Prescription expenditures in clinics and nonfederal hospitals totaled $63.7 billion (an 11.9% increase from 2015) and $34.5 billion (a 3.3% increase from 2015), respectively. In nonfederal hospitals and clinics, growth in spending was driven primarily by price increases of existing drugs and increased volume, respectively.We project a 6.0–8.0% increase in total drug expenditures across all settings, an 11.0–13.0% increase in clinics, and a 3.0–5.0% increase in hospital drug spending in 2017. Health-system pharmacy leaders should carefully examine their own local drug utilization patterns to determine their own organization's anticipated spending in 2017.