Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10 km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP (p = 0.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model.