Abstract Background Ginseng is a perennial herb used in traditional Chinese medicine, which has become increasingly popular world-wide due to its proposed medicinal effects. There are two major species of ginseng, Panax ginseng (Korean or Asian ginseng), and Panax quinquefolius (American ginseng). Although cases of allergy due to Korean ginseng have been reported in adults, there are no reported cases of allergy to American ginseng, and no reported cases of ginseng allergy in pediatric patients. Case presentation We present two unique cases of pediatric patients with suspected allergic reactions to American ginseng. The first patient is a 6-year-old girl who presented to the emergency department in anaphylaxis (urticaria and respiratory symptoms) minutes after inhaling powdered American ginseng. There was evidence of sensitization to American ginseng on skin prick testing (SPT) (13 × 12 mm wheal) and evidence of allergy to American ginseng on basophil activation testing, with a dose-dependent increase in expression of CD63 on basophils in response to American ginseng extract. The second patient is a 3-year-old boy who presented with recurrent allergic conjunctivitis upon exposure to aerosolized powdered ginseng, with evidence of sensitization to American ginseng on SPT (13 × 7 mm wheal), but with no evidence of IgE-mediated allergic reaction during oral challenge with American ginseng powder. Conclusions These cases highlight two different allergic responses to American ginseng in pediatric patients. To our knowledge, these are the first reported cases of allergy to American ginseng, in addition to the first reported cases of allergy to ginseng in pediatric patients.