Introduction: Peripheral arterial disease (PAD) is an occlusive atherosclerotic disease of the arteries of the extremities of the body that affects more than 230 million people worldwide. The most common symptom is intermittent claudication, described as leg pain which occurs mainly while walking. The symptoms impair the ambulation and functional capacity of patients, leading to loss of mobility, disease deterioration, increased risk of other cardiovascular diseases, and lower quality of life (QoL). Therefore, the aim of this study was to perform a cross-cultural adaptation and validation of the VascuQol-6 questionnaire for the Portuguese population to obtain a quick, sensitive, and easy-to-use way to assess the QoL of Portuguese patients diagnosed with PAD. Methods: The Vascular Quality of Life-6 Questionnaire (VascuQoL-6) was adapted and translated into European Portuguese using standard validation methodology, including 115 patients with a mean age of 64.67 (7.23) years, with PAD with IC stable for more than three months; and ABI < 0.9 at rest. VascuQoL-6, SF-36, International Physical Activity Questionnaire (IPAQ), and the PAD Knowledge Questionnaire (PADKQ) were used. Reliability, construct validity analysis through convergent and discriminant validity, known-group validity, and responsiveness analysis were tested. Results: The Cronbach’s alpha was 0.64 and the average inter-item correlation was 0.27, indicating acceptable internal consistency. VascuQoL-6 was positively associated with SF-36 Physical Component Summary and Mental Component Summary scores (r = 0.64, p < 0.01 and r = 0.42, p < 0.01, respectively). In turn, there was no significant correlation between VascuQoL-6 scores and the PADKQ or IPAQ. A statistically significant difference between groups according to IC severity [F(2.47) = 8.35, p < 0.001] was found. A paired samples t-test showed differences between VascuQol-6 scores before a walking program (M = 15.65, SD = 3.09), and after a walking program (M = 17.41, SD = 2.71), t(67) = 3.94, p ≤ 0.001. Conclusion: The VascuQoL-6 is a six-item instrument to assess the QoL associated with PAD with good psychometric properties, convergent and discriminant validity with SF-36, PADKQ and IPAQ. The instrument proved to have known group validity and responsiveness.