OBJECTIVES:To determine which demographic, amputation, and health-related factors were associated with health-related quality of life (HR-QoL) in people living with partial foot amputation (PFA) or transtibial amputation (TTA). DESIGN:Cross-sectional survey. SETTING:Community. PARTICIPANTS:Adults (N=123) with unilateral PFA (n=42) or TTA (n=81). INTERVENTION:Not applicable. MAIN OUTCOME MEASURE:Medical Outcome Short Form (SF-36) version 2. RESULTS:Variation in the SF-36 Physical or Mental Component Summary scores were associated with complex interactions between factors, including: time since amputation, fatigue, anxiety, depression, pain interference, and physical function. Level of amputation (ie, PFA or TTA) did not explain a significant part of the variation in either the SF-36 Physical or Mental Component Summary scores. CONCLUSIONS:Given the complex interactions between factors associated with the physical and mental health components of HR-QoL, there are opportunities to consider the long-term holistic care required by people living in the community with PFA or TTA.