IMPORTANCE: Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death. OBJECTIVE: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture. POPULATION: Adults 40 years or older without known osteoporosis or history of fragility fractures. EVIDENCE ASSESSMENT: The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older has moderate net benefit. The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk has moderate net benefit. The USPSTF concludes that the evidence is insufficient and the balance of benefits and harms for screening for osteoporosis to prevent osteoporotic fractures in men cannot be determined. RECOMMENDATION: The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older. (B recommendation) The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years who are at increased risk for an osteoporotic fracture as estimated by clinical risk assessment. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men. (I statement).