Objective. The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly. Design, Patients, and Methods. 52 acromegaly patients (mean age 45.7 +/- 1.9 years) and 83 controls (mean age 43.1 +/- 2.6 years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods. Results. The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P = 0.034). VDR FokI ff genotype was significantly decreased in acromegaly patients (P = 0.035) and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07-2.1; P = 0.020). IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P = 0.0049). 25(OH) D3 levels were significantly lower in acromegaly patients (P < 0.001). Conclusions. Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status.