Background: The five base-pair (bp) insertion/deletion (rs3039851) polymorphism in thePPP3R1gene, which encodes calcineurin subunit B type 1, has been found to be associated with left ventricular hypertrophy (LVH) in hypertensive patients and in athletes. The aim of this study is to analyze the possible association betweenPPP3R1:rs3039851 polymorphism and left ventricular mass (LVM) in full-term healthy newborns. Methods: The study group consisted of 162 consecutive, full-term, healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM. ThePPP3R1:rs3039851 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. Results: No significant differences were found between newborns homozygous for the reference allele (5I/5I, n = 135) and newborns carrying at least one 5D allele (n = 27) for LVM standardized for body mass, body length or body surface area (LVM/BM, LVM/BL or LVM/BSA, respectively). However, the frequency ofPPP3R1:rs3039851 genotypes with a 5D allele (5I/5D + 5D/5D) among newborns with the largest LVM/BM or LVM/BSA (upper tertile) was statistically significantly higher compared with the prevalence in individuals with the lowest values of both indices (lower tertile). Conclusions: Our results suggest that thePPP3R1:rs3039851 polymorphism may contribute to subtle variation in left ventricular mass at birth.