Aim: This study investigates the effect of time and age on health-related quality of life, general self-efficacy, and functional level 12 months following dysvascular major lower limb amputation (LLA). Methods: A prospective cohort study design with assessments at baseline and follow-up 3, 6, and 12 months post-amputation. Data were collected via in-person interviews using Short Form 36, the General Self-efficacy scale and Barthel Index 100. Out of a consecutive sample of 103 patients having dysvascular major LLA (tibia, knee, or femoral), 38 patients completed the study. Outcome at follow-up was compared with baseline and analyzed in age groups. Results: All SF36 subscale scores were below population norms at baseline. At 12 months, two out of eight scores—physical function and role-physical—had not improved. Different patterns of change over the 12 months were detected among the subscales, and psychosocial problems persisted and fluctuated throughout the 12 months in all age groups. Large differences were identified between age groups in physical function with the loss of physical function almost solely evident among the oldest (aged 75+ years) patients. Conclusions: Special attention should be given to the oldest patients need for rehabilitation so that they gain higher quality of life.