Objective: Hypoplastic left heart syndrome is a major congenital heart defect and is associated with significant morbidity and mortality. Its etiology remains unknown although genetic studies imply complex inheritance. Anecdotal reports of cluster presentations suggest the possible involvement of an environmental component, although previous epidemiologic studies have been of limited scope. The objective of this study was to examine seasonal and temporal patterns of hypoplastic left heart syndrome births compared with other left-sided heart defects in the United States. Methods: We conducted a retrospective analysis of the Pediatric Health Information System inpatient database from pediatric hospitals across the country from 1996 to 2006. Population and index case patterns were analyzed for each diagnostic category. An epidemiologic survey was performed through time-series analyses using Fisher's Kappa test and the Bartlett Kolmogorov-Smirnov test. The existence and strength of seasonality for the left-sided heart defects was quantified by the autoregression R2. Results: A seasonal occurrence was found in hypoplastic left heart syndrome but not other left-sided heart diseases. Significant seasonal differences occurred each year, with peaks in summer months and troughs in winter months. The seasonality inversely correlated with the incidence of chromosomal and extracardiac anomalies; such anomalies were highest in interrupted aortic arch, which had a random pattern of presentation. Conclusions: There is a significant seasonal pattern in the presentation of hypoplastic left heart syndrome, with preponderance in summer months, in contrast to the random pattern in other left-sided heart diseases. Further studies are warranted to identify the influence of potential environmental factor(s) in hypoplastic left heart syndrome, as seen in diseases with seasonal patterns.