Importance: Different screening strategies for breast cancer are available but have not been researched in quantitative detail. Objective: To assess the benefits and the harms of risk-based and universal mammography screening in comparison with annual clinical breast examination (CBE). Design: Population-based cohort study comparing incidences of stage II+ disease and death from breast cancer across 3 breast cancer screening strategies, with adjustment for a propensity score for participation based on risk factors for breast cancer and comparing the 3 strategies for overdetection between January 1999 and December 2009. Asymptomatic women attending outreach screening in the community or undergoing mammography in hospitals were enrolled in the 3 screening programs. Interventions: Risk-based biennial mammography, universal biennial mammography, and annual CBE. Main Outcomes and Measures: Detection rates, stage II+ disease incidence, mortality from breast cancer, and overdiagnosis were compared using a time-dependent Cox proportional hazards regression model. Results: A total of 1 429 890 asymptomaticwomen attending outreach screening in the community or undergoing mammography in hospitalswere enrolled in the 3 screening programs. Detection rates (prevalent screen and subsequent screens per 1000)were the highest for universal biennial mammography (4.86 and 2.98, respectively), followed by risk-based mammography (2.80 and 2.77, respectively), and lowest for annual CBE (0.97 and 0.70, respectively). Universal biennial mammography screening, compared with annual CBE, was associated with a 41% mortality reduction (risk ratio, 0.59; 95%CI, 0.48-0.73) and a 30% reduction of stage II+ breast cancer (RR, 0.70; 95%CI, 0.66-0.74). Risk-based mammography screeningwas associated with an 8%reduction of stage II+ breast cancer (RR, 0.92; 95%CI, 0.86-0.99) butwas not associated with a statistically significant mortality reduction (risk ratio [RR], 0.86; 95%CI, 0.73-1.02). Estimates of overdiagnosiswere no different from CBE for risk-based screening and 13%higher than CBE for universal mammography. Conclusions and Relevance: Compared with population-based screening for breast cancer with annual CBE, universal biennial mammography resulted in a substantial reduction in breast cancer deaths, whereas risk-based biennial mammography resulted in only a modest benefit. Compared with annual CBE, risk-based and universal mammography screening did not result in significant overdiagnosis of breast cancer.