Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance as the sole option for men with low-risk prostate cancer (LRPC) and a life expectancy <10 years. We sought to describe the incidence, risk factors, cost, and morbidity related to overtreatment of LRPC within the United States. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare Program to identify 11,744 men ≥66 years with LRPC diagnosed from 2004-2007. Expected survival was estimated using the 2007 Social Security Life Table and was increased and decreased by 50% in men in the upper and lower quartiles of comorbidity, respectively, as specified by the NCCN. Overtreatment was definitive treatment in men with LRPC and life expectancy <10 years. Costs were the amount paid by Medicare in the year following minus the year prior to diagnosis. Toxicities were defined as relevant Medicare diagnoses or interventions. Results: Of 3001 men with LRPC and a life expectancy <10 years, 2011 (67%) were treated definitively. On multivariable logistic regression, men overtreated for prostate cancer were more likely to be younger (p<.001), white (vs black, OR 1.44, 95% CI 1.03-2.02, p=.03), married (OR 1.30, 95% CI 1.05-1.61, p=.02), urban (trend, OR 1.40, 95% CI 0.98-2.00, p=.06), have higher Elixhauser comorbidity (p<.001), and have a higher clinical stage (T2 vs T1, OR 1.57, 95% CI 1.19-2.07, p=.001) and prostate-specific antigen level (OR 1.02, 95% CI 1.02-1.02, p<.001). Relative to expectant management, the mean added cost per definitive treatment was $15,308. When extrapolated nationally the cumulative net cost of overtreatment in men ≥66 years is $32 million per annum. Long-term urinary, erectile, and bowel toxicity occurred in 59.2% and 50.0%, 47.9% and 19.7%, and 7.1% and 17.8% of prostatectomy and radiation patients, respectively. Conclusions: Overtreatment of prostate cancer is partially driven by sociodemographic factors and occurs in a high percentage of men with LRPC and limited life expectancy, with marked impact on patient quality of life and health care costs. Efforts to enhance appropriate management of LRPC would reduce the harms associated with screening.