Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. Objective: To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. Design: Simulation of life histories using Markov health states. Data Sources: Childhood Cancer Survivor Study; published literature. Target Population: Childhood cancer survivors. Time Horizon: Lifetime. Perspective: Societal. Intervention: Echocardiographic screening followed by angiotensinconverting enzyme (ACE) inhibitor and β-blocker therapies after ALVD diagnosis. Outcome Measures: Quality-Adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. Results of Base-Case Analysis: The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. Results of Sensitivity Analysis: The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. Limitation: Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and -blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). Conclusion: The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more costeffective than the COG guidelines. Primary Funding Source: Lance Armstrong Foundation and National Cancer Institute. © 2014 American College of Physicians.