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Background: Craniosynostosis is a relatively common congenital abnormality. The underlying etiology and most probable risk factors of nonsyndromic craniosynostosis are unknown. We conducted a study to identify the risk factors for craniosynostosis. Materials and Methods: In this case-control project, 70 children with craniosynostosis (syndromic or nonsyndromic) hospitalized at the Children's Hospital Medical Center from September 2010 to 2011 were studied for the potential risk factors. At the same time, 70 age- and sex-matched children hospitalized with other congenital anomalies were reviewed. Information from case and control groups was obtained via personal interviews with parents of patients and a prepared checklist was filled out for each child. Results: The mean (±SE) age at admission time in the case-control group was 13 ± 1.95 (1.5-96) months, and almost half of them were boys (n = 37 or 53%). The most frequent sutures involved in craniosynostosis were coronal (n = 30 or 42.9%) and then metopic sutures (n = 16 or 22.9%), multiple (n = 12 or 17.1%), sagittal (n = 11 or 15.7%) and lambdoid (n = 1 or 1.4%). In the case group, maternal diabetes mellitus and thyroid disease were found in 8 (11.6%) and 6 (8.6%) patients, respectively. The most frequent medication used by mothers (n = 66 or 94%) in the case group during pregnancy were vitamins (including iron supplements, omega 3, folic acid and multivitamins). Conclusion: A positive family history of craniosynostosis [odds ratio (OR) 19.01 and 95% confidence interval (CI) 2.24-160.7] and using clomiphene citrate for infertility (OR 12.71 and 95% CI 1.42-113.6) were the strongest independent risk factors for craniosynostosis. More comprehensive studies with a larger sample size are required to confirm the role of environmental factors in order to decrease the occurrence of craniosynostosis.