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In 2012 the American Urological Association released asymptomatic microhematuria guidelines that resulted in criticisms of overtreatment and improper risk stratification, particularly in women. Specifically, concerns have been raised regarding overtreatment in low risk female patients. Evaluating trade-offs between cost and effectiveness can provide valuable insight into the applicability of these guidelines in different patient populations.We used a decision analysis model to estimate the cost-effectiveness of a microhematuria evaluation according to the 2012 guidelines, using varying strategies according to whether confirmatory urinalysis was obtained and stratifying by sex. Where applicable, model parameter values were from prospective observational trials. Costs were estimated based on U.S. databases.Up-front evaluation costs 20% more than confirmatory evaluation ($792.76 vs $662.65). When considering costs per quality adjusted life-year, up-front evaluation costs $125,105 per quality adjusted life-year gained in the overall population. When stratified by sex, up-front evaluation costs $94,777 per quality adjusted life-year gained in male patients and $390,954 per quality adjusted life-year gained in female patients. At a cost-effectiveness threshold of $100,000 per quality adjusted life-year, up-front evaluation is cost-effective in male but not in female patients or the overall population compared to a delayed evaluation.Up-front microhematuria evaluation may be economically justifiable in men but not in women or in the overall population. Sex specific risk stratification and confirmatory urinalyses may have a role in populations with a lower risk of urinary tract malignancy.