Preterm birth is the most common reason for perinatal morbidity and mortality in the western world. It has been shown that in euthyreotic pregnant women with thyroid autoimmune antibodies, L-Thyroxine replacement reduces preterm delivery rate in singleton pregnancies. We investigated in a nonrandomized retrospective observational study whether L-Thyroxine replacement, maintaining maternal free thyroxine serum level in the high normal reference range prescribed for nonpregnant women also influences the rate of preterm delivery in women without thyroid autoimmune antibodies. As control group for preterm delivery rate, data from perinatal statistics of the State of Baden-Württemberg from 2006 were used. The preterm delivery rate in the study group was significantly reduced. The subgroup analysis shows no difference in primiparous but a decline in multiparous by approximately 61% with L-Thyroxine replacement. Maintaining free thyroxine serum level in the high normal reference range prescribed for nonpregnant women may reduce the preterm delivery rate.