Twenty-four hands have been transplanted in 18 individuals and clinicians continue to debate whether the risks justify the benefits in these procedures. To assess quantitatively the risks versus benefits in hand transplantation we used a validated instrument (Louisville Instrument for Transplantation) to measure the degree of risk individuals are willing to accept to receive different types of transplantation procedures. The Louisville Instrument for Transplantation contains 237 standardized questions that incorporate modified standard gamble and time trade-off outcome measures and questions that assess body image perception, depression, self-esteem, optimism, socially desirable responding, and demographics. Respondents were questioned on the extent to which they would trade off specific numbers of life-years or sustain other costs in exchange for receiving 7 different transplantation procedures. For this study we questioned 227 individuals in 4 study populations with differing life experiences: healthy individuals, organ transplant recipients, upper-extremity amputee patients, and lower-extremity amputee patients. All populations questioned perceived risk similarly despite their differing life experiences and would accept differing degrees of risk for the different transplantation procedures. Organ transplant recipients were the most risk-tolerant group whereas upper-extremity amputee patients were the most risk adverse, even when considering a single hand transplant. All groups that were questioned would accept a higher degree of risk to receive a double versus a single hand transplant. By questioning individuals who have experienced directly the risks of immunosuppression and those who could benefit from hand transplantation, this study presents an empiric basis for assessing risk versus benefit in this procedure.