Objectives:To analyze the possible gender differences within the clinical risk profile of lower-limb amputee patients who had a non-traumatic amputation. Method: A retrospective study with 697 lower-limb amputee patients, classified according to their gender, has been conducted at the Angiology and Vascular Surgery Department for 5 years. The variables considered were demographic variables (age and gender) and clinic variables (cause of the amputation, comorbidity, cardiovascular risk factors and the amputation level). Results: Regarding to the results, the average of women was older than men (75.3 ± 12 vs. 68.9 ± 11 years; p < 0.001), showing an increasing frequency to concomitant cardiovascular risk factors, such as diabetes, hypertension, and obesity. However, men present a higher frequency to smoking. There were no gender differences in the main cause of the amputation, the ischemic cause, being notably into this cause the subgroup of arteriosclerosis cause. Women showed a higher frequency and predisposition for major amputation. Conclusions: This study showed that women had a more unfavorable cardiovascular risk profile than men, being the female gender an independent predictor to a major lower-limb amputation with non-traumatic amputation.