Purpose To assess the clinical and cost-effectiveness of allografts versus autografts in the reconstruction of anterior cruciate ligaments. Methods Systematic review of comparative clinical effectiveness and cost-effectiveness analysis. Results Both autograft and allograft reconstruction are highly effective. Recent studies show little difference in failure rates between autografts and allografts (about 6% and 7%, respectively). In cost-effectiveness analysis, the price differential is the main factor, making autografts the first choice. However, there will be situations, particularly in revision ACL reconstruction, where an allograft may be preferred, or may be the only reasonable option available. Conclusion In ACL reconstruction, clinical results with autografts are as good as or slightly better than with allografts. Allografts cost more, indicating that autografts are more cost-effective and should usually be first choice. Level of evidence II.