Background: Carpal tunnel syndrome (CTS) is a common neurologic impairment caused by injury on the median nerve in the wrist, characterized by pain and loss of sensory. CTS usually occurs through three factors, such as a mechanical pressure on median nerve, immunologic changes, and oxidative stress. The aim of this study was to evaluate the influence of interleukin-1 receptor antagonist (IL-1Ra) and angiotensin-converting enzyme (ACE) I/D polymorphisms on the susceptibility of patients to the CTS. Methods: One hundred fifty-eight patients with CTS and 151 healthy controls were enrolled in this study. Each patient was analyzed according to diseases symptoms, such as gender, a positive Tinel's sign, a positive Phalen maneuver, disease sides, EMG findings, and clinical stage. We applied the polymerase chain reaction (PCR) to determine the polymorphisms of IL-1Ra and ACE I/D. Results: The statistically significant relation was not found between IL-1Ra, ACE I/D polymorphisms and CTS (respectively, P>.05; P>.05, OR: 1.51, CI: 0.82-1.61). Additionally, in the result of the statistical analysis compared with gene polymorphisms and clinical characteristics, we did not find any correlation (P>.05). Conclusions: Our findings showed that there are no associations of IL-1Ra and ACE I/D polymorphisms with susceptibility of a person for the development of CTS. So, it means that these polymorphisms do not create a risk for the development of CTS. Further studies with larger populations will be required to confirm these findings in different study populations.