Methotrexate is an immunomodulator used as first line treatment for patients with rheumatoid arthritis and has a well-recognized association with other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD). OIIA-LPD and its association with methotrexate has been discussed in the literature but is rarely seen in the pediatric population. Additionally, there are no prior reports showing an association between IIA-LPD and bacterial superinfection. We present a case of airway compromise requiring emergent tracheostomy in a 15-year-old patient secondary to superimposed infection in the setting of lymphoproliferative disorder. To our knowledge, this is the first case of OIIA-LPD causing airway compromise requiring emergent tracheostomy.