Major amputation of a lower limb is a traumatic experience that causes physical and psychosocial disabilities. This study set out to ascertain how anxiety and depression symptoms changed during the three months following the amputation. A prospective longitudinal observational study was conducted between October 1, 2019, and January 1, 2021, in the Department of Vascular Surgery and the Department of Orthopedic Traumatology of the Ibn Sina Hospital Center in Rabat, Morocco. The study assessessymptoms of anxiety and depression in patients who have undergone a major lower limb amputation over a three-month interval. In patients who had undergone a major lower limb amputation, the prevalence of anxiety and depression symptoms was very high immediately postoperatively (47.4% and 79.2%, respectively), with a significant decrease in these symptoms. Three months later, anxiety was reported in 24.4% of cases, and depressive symptoms in 65.1% of cases. Age, amputation level, stump pain, phantom limb pain, re-amputation, and emergency amputation were all associated with an increased risk of anxiety and depression. The patient's psychological preparation prior to the amputation, the anesthetic technique used during the procedure, the patient's mobility, and the patient's post-amputation professional status were all protective factors. Our research findings bolster the necessity of promptly evaluating and managing anxiety and depression in the initial three months following major lower limb amputation. Thus, we believe that amputee patients ought to receive a formal psychological evaluation, which could be helpful, particularly for those whose anxiety or depression symptoms did not improve after three months.