BACKGROUND: Lower limb amputation is a major medical and public health concern, with consequences extending beyond the physical loss of a limb. Patients face substantial physical, emotional, and social challenges that significantly impact their quality of life. This study aimed to assess the impact of amputation on quality of life and to compare outcomes between younger and older patients. METHODS: A cross-sectional study was conducted at Dubrava University Hospital, including 30 patients (15 men, 15 women) who underwent lower limb amputation. The most common comorbidities were peripheral vascular disease and diabetes mellitus. Participants were divided into two age groups (18–65 years; ≥66 years). Data were collected using the WHOQOL-BREF questionnaire and the Social Support Scale. Descriptive statistics and the Mann–Whitney U test were applied. RESULTS: Older patients reported significantly poorer quality of life (U = 21.00, p < 0.001), reduced physical functioning (U = 14.50, p < 0.001), more pronounced negative emotional symptoms (U = 47.50, p = 0.007), and lower perceived social support (U = 22.50, p < 0.001). Pain levels declined over time, and satisfaction with rehabilitation programs was positive, with no significant differences between age groups. CONCLUSION: Age is a key determinant of quality of life after amputation. Older patients face multiple challenges, underscoring the need for an individualized, multidisciplinary, and holistic rehabilitation approach that integrates medical, psychological, and social support.