Post-thrombotic syndrome (PTS) impacts the patient's quality of life. Available scales to determine its severity remain controversial, therefore, it is of importance to identify new auxiliary methods for the assessment of this sequelae. Measurement of skin hardness (MSH) might be decisive in tracking PTS. The purpose of this study is to assess if the use of durometry is an objective measure to evaluate prognosis of affected limbs in patients with PTS. We compared MSH of extremities with PTS vs healthy limbs, as well as their variation after 3 months of medical treatment to evaluate if durometry can be used to find differences. We strongly believe that measuring and keeping track of skin changes specifically skin hardness can be a useful factor in the prognosis and treatment of PTS. Prospective cohort study from January 2021 to February 2022 in patients with unilateral PTS. The MSH of the affected limb was compared to the healthy limb. A calibrated durometer was used, 4 measurements were completed at the time of diagnosis and subsequent follow-up were carried out after 3 months of treatment. The percentage of healing (in case of ulcers) and adherence to treatment was carefully monitored. The statistical program R was used. A total of 1088 durometric measurements were performed on 17 patients, and 34 limbs. The MSH in limbs with PTS was 39.09 and in the control limbs (19.8) (P = <.00001). After 3 months of treatment, the MSH in PTS varied in PTS limbs (39.09 to 30.4) (P = <.000012). Adherence to treatment was 70.5%. MSH varied between healthy limbs and the ones with PTS, before and after treatment. Durometry might represent a method for assessing skin changes in patients with PTS.