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Background: Interpregnancy interval is a risk factor for various adverse birth outcomes including birth defects. We investigated the relationship between interpregnancy interval and birth defects., Methods: We conducted a retrospective cohort study using linked data from Nevada Birth Outcomes Monitoring System and birth certificate data for 124,341 singleton live births, of which 4641 infants had 7192 birth defects, among Nevada resident women between 2006 and 2011. We used logistic regression to assess factors independently associated with birth defects., Results: Women who had an interpregnancy interval of 36 months or more, adjusted odds ratio (AOR) = 1.16, 95% confidence interval [CI], 1.01-1.33, were more likely to have an infant with a birth defect compared with women with an interpregnancy interval of 18 to 23 months. Other independent risk factors for birth defects included male infants, AOR = 1.34, 95% CI, 1.26-1.42; maternal age (30-34 years) and advanced maternal age (35 years and older), AOR = 1.10, 95% CI, 1.01-1.19 and AOR = 1.29, 95% CI, 1.18-1.42, respectively; being a Black woman, AOR = 1.46, 95% CI, 1.32-1.61; three and four or more previous births, AOR = 1.12, 95% CI, 1.02-1.23 and AOR = 1.24, 95% CI, 1.11-1.38, respectively; smoking, AOR = 1.23, 95% CI, 1.10-1.38; and prescription drug use, AOR = 1.14, 95% CI, 1.07-1.21., Conclusion: A long interpregnancy interval is an independent risk factor for birth defects. It may be helpful for maternal and child health programs and health care providers to highlight the deleterious effects of a long interpregnancy interval., (© 2015 Wiley Periodicals, Inc.)