Automated monitoring of the QT interval is increasingly common in a variety of clinical settings. A better understanding of how the heart-rate-corrected QT interval (QTc) evolves in early postnatal life is needed before its clinical utility in neonates can be determined. This study aimed to use real-time bedside monitoring as a tool to describe the QTc evolution of premature neonates during the first week of life. All neonates born at a gestation age (GA) of 31 weeks or later and admitted to the level 2 intensive care nursery of the authors’ institution between December 2012 and March 2013 were included in this study. The authors prospectively collected QTc values at 15-min intervals during the first week of life, then used two-way analysis of variance (ANOVA) to compare these data among three GA cohorts: 31 to <34 weeks (cohort A), 34 to <37 weeks (cohort B), and ≥37 weeks (cohort C). All the cohorts demonstrated a statistically significant decline in the 24-h average QTc during the first 3–4 days of life before reaching a stable baseline. No diurnal variation in the QTc was identified in any of the study patients. Marked variability and a progressive decline in the QTc of premature neonates occur during the first 3–4 days of life. Understanding this phenomenon is imperative when screening programs for the early detection of QT prolongation are considered.