Diagnosis of syn/chrom or major comorbidity significantly increases risk of G-tube placement. Regardless of syn/chrom association, problems affecting the heart, respiratory system, central nervous system, and lower esophageal sphincter are the most significant risk factors, implying that particular comorbidities are more influential than a simple diagnosis of syn/chrom. These data should help identify children at greatest risk for G-tubes and those expected to overcome feeding difficulties, leading to more persistent use of nonsurgical therapy before resorting to G-tubes.