Objective: (1) To identify significant changes in disability and quality of life (QoL) across three time points (T1 = admission to rehabilitation, T2 = six weeks post-discharge, T3 = six months post-discharge) in individuals with lower limb amputation, and (2) to examine whether goal pursuit and goal adjustment at T1 were predictive of these outcomes at T3. Design: Prospective cohort study. Setting: Inpatient rehabilitation. Participants: Consecutive sample of 64 persons aged 18 years and over with major lower limb amputation. Interventions: Not applicable. Main Outcome Measures: World Health Organisation Disability Assessment Schedule Version 2.0 (WHODAS 2.0); World Health Organisation Quality of Life Questionnaire-Brief Version (WHOQOL-BREF). Results: Mean WHODAS 2.0 scores were in the 95th percentile at each time point. Scores on the WHODAS 2.0 and the physical, psychological and social relationships domains of the WHOQOL-BREF remained stable across the study period. Environmental QoL scores decreased from T1 to T2, but returned to near-baseline levels between T2 and T3. Having a greater tendency towards goal pursuit at T1 was predictive of higher physical and psychological QoL at T3, while having a stronger disposition towards goal adjustment at T1 predicted lower disability and higher environmental QoL at T3. Conclusions: High levels of disability were experienced from admission to rehabilitation up to six months post-discharge. QoL in the physical, psychological and social relationships domains remained stable over the study period. Stronger goal pursuit and goal adjustment tendencies on admission predicted lower disability and higher QoL six months post-discharge.