Objective: Fibromyalgia syndrome (FM) is a common disease characterized by generalized body pain, sensitivity in certain physical areas (sensitive points), lowered pain threshold, sleep disorder, and fatigue. The study aimed to determine the effects ACE I/D and MTHFR C677T gene polymorphisms in Turkish patients with FM and evaluate if there was an association with clinical features. Methods: This study included 200 FM patients and 190 healthy controls recruited from the department of Physical Medicine and Rehabilitation at Gaziosmanpasa University in Tokat, Turkey. ACE I/D polymorphism genotypes were determined by using polymerase chain reaction (PCR) by specific primers. The MTHFR C677T mutation was analyzed by PCR-based restriction fragment length polymorphism (RFLP) methods. Results: We found a statistically significant relation between ACE polymorphism and FM (p. <. 0.001, OR: 1.71, 95% CI: 1.28-2.27). However, this was not the case for ACE polymorphism and the clinical characteristics of the disease. There was also no statistically significant relation between MTHFR C677T mutation and FMS (p > 0.05, OR: 1.20, 95% CI: 0.82-1.78), but dry eye and feeling of stiffness which are among the clinical characteristics of FMS were significantly related with MTHFR C677T mutation (p. <. 0.05). Conclusion: Our findings showed that there are associations of ACE I/D polymorphism with susceptibility of a person for development of fibromyalgia syndrome. Also, it is determined an association between MTHFR C677T polymorphism and feeling of stiffness and dry eye which are among the clinical characteristics of FM. Our study is the first report of ACE I/D and MTHFR C677T polymorphisms in fibromyalgia syndrome.