Cost-effectiveness information can help health-system participants make decisions about diagnostic or therapeutic innovations that are more expensive but incrementally safe and effective. However, these analyses cannot help decide whether a less expensive approach is “sufficient” and funds ought to be allocated to other medical issues entirely. At present, formulary committees are commonly determining that medications are “mostly equivalent” in efficacy and safety and choosing individual medications or classes of medications based on cost. Clinicians may not agree with these decisions and will need to understand their rationale. For prophylaxis of venous thromboembolism after hip and knee replacement and hip fracture surgery, many preventive modalities are available with different safety and efficacy profiles and different costs. It is possible to list the important safety and efficacy outcomes of prophylaxis, estimate their incidences and costs, and “model” comparisons of one modality vs another, in order to help decide whether one is preferable.