Background: Chronic urticaria (CU) is a common skin condition, affecting 0.5-1% of the population. Multiple studies have demonstrated that plasma D-dimer levels could be employed as a biomarker for disease activity and treatment response in patients with CU. Aim: The aim was to evaluate the correlation between D-dimer levels and the disease activity of CU. Materials and Methods: This study was a case-control study conducted on 120 patients suffering from CU and 50 healthy subjects. Plasma D-dimer levels were measured using ELISA. Results: Mean plasma D-dimer levels in the patients with CU (720.5 ng/mL) were significantly higher than those in the controls (405.6 ng/mL) (p < 0.001). A significant correlation was observed between plasma D-dimer levels and the UAS (urticaria activity score). Conclusion: The patients with CU had higher plasma D-dimer levels than the control group. A positive statistical correlation was observed between plasma D-dimer levels and the severity of CU.