The objective of this study is to evaluate the yield of genetic testing in infants with congenital heart disease, who undergo surgical intervention prior to one year of age, and develop a cost-effective strategy to screen infants with congenital heart disease for genetic conditions while providing standard of care. 409 charts of patients with congenital heart disease, who underwent surgical intervention prior to one year of age, were retrospectively reviewed for cytogenetic testing results. 278 patients underwent cytogenetic testing, and 89.6 % of these patients had more than one cytogenetic test completed. The most commonly encountered chromosomal anomaly within the sample was Down Syndrome (12.5 %), followed by 22q11.2 Deletion Syndrome (4.6 %). G-Banded Karyotypes were abnormal in 10.5 % of patients, fluorescence in situ hybridization (FISH) probe for 22q11.2 deletion was abnormal in 7.1 % of patients. SNP microarray testing showed the highest yield and was abnormal in 33 % of patients. Based on the data at our institution, a more directed approach of genetic screening with only microarray would have saved our institution approximately $101, 200 on the 103 patients who underwent genetic evaluation with microarray reviewed. Screening infants with congenital heart disease for 22q11.2 deletion with FISH resulted in a loss of approximately $32,000 per 100 patients at our institution. Institutions should develop microarray-based protocols for genetic screening in patients with congenital heart disease with the anticipation of adding lesion-specific single gene testing as single gene testing becomes routinely available.