BACKGROUND: Evaluating the effectiveness of a novel prosthetic device during walking is an important step in product development. OBJECTIVE: To investigate the efficacy of a novel quasi-passive ankle prosthetic device, Ankle Mimicking Prosthetic Foot 4.0, during walking at different speeds, using physiological determinants in transtibial and transfemoral amputees. STUDY DESIGN: Nonrandomized crossover design for amputees. METHODS: Six able-bodied subjects, six unilateral transtibial amputees, and six unilateral transfemoral amputees underwent a 6-min walk test at normal speed, followed by series of 2-min walking at slow, normal, and fast speeds. The intensity of effort and subjective measures were determined. Amputees performed all walking tests on a treadmill with current and novel prostheses. Shapiro-Wilk normality tests and parametric and nonparametric tests were conducted (p < 0.05). RESULTS: Compared to able-bodied individuals, the rating of perceived exertion levels were significantly elevated in transtibial and transfemoral amputees for both prostheses (p ≤ 0.016). Compared to able-bodied individuals transfemoral amputees also showed significantly elevated heart rate for both prostheses at normal speed (p ≤ 0.043). Within-group comparisons demonstrated that walking with Ankle Mimicking Prosthetic Foot significantly increased the heart rate in transfemoral amputees and transtibial compared to current prosthesis (p = 0.002). Furthermore, transfemoral amputees reached a significantly higher rating of perceived exertion levels. CONCLUSION: Intensity of effort during walking with Ankle Mimicking Prosthetic Foot is higher compared to current prostheses. Clinical relevance Ankle Mimicking Prosthetic Foot 4.0 is a novel quasi-passive ankle prosthesis with state-of-the-art technological parts. Subjective measures show the importance of this technology, but the intensity of effort during walking still remains higher compared to current passive prostheses, especially in transfemoral amputees.