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The objectives of this study are to investigate the relationship between adjustments to amputation and artificial limb, and quality of life (QoL), and to analyse the influence of sociodemographic, medical and amputation-related factors on this relationship. Patients with unilateral and noncongenital lower limb amputation who were using artificial limb were interviewed (n=368) using structured questionnaires. The Trinity Amputation and Prosthesis Experience Scales (TAPES) were used to assess adjustments to amputation and artificial limb and the MOS Short-Form Health Survey (SF-36) was used to assess the physical (PCS) and mental (MCS) component summary of QoL. Absence of comorbidity and residual stump pain, being employed, young age, less functional restriction, being more adjusted to limitation, increased social adjustment and less restriction in athletic activity were related to better PCS scores. Absence of comorbidity and phantom limb pain, nonuse of assistive device, being more adjusted to limitation, increased social adjustment and being less functionally restricted were related to higher MCS scores. Comorbidity had a modifying effect on both PCS and MCS scores. In addition, age, being employed and residual stump pain had a modifying influence on PCS, whereas assistive device use and phantom limb pain had a modifying influence on MCS. Our findings show that TAPES subscales have a modifying effect on the associations between several background (sociodemographic and amputation characteristics) and QoL (PCS and MCS). This indicates that adjustments to amputation and artificial limb are the key determinants of QoL in individuals following lower limb amputation.