Background: Peanut allergy is a major health burden in the United States. Treatment is limited to avoidance and acute reaction management. No drug or medical product is approved for use as a peanut oral immunotherapy (POIT) agent. Objective: To examine peanut allergy diagnosis and treatment, peanut challenge protocols, nonpublished POIT approaches, POIT practice requirements and logistical considerations, and barriers to providing POIT. Methods: Qualitative in-depth telephonic interviews were conducted with 34 allergists and nurse food allergy specialists across the United States between April and June 2016. Interviewed clinicians managed > 100 patients with peanut allergy per year; 50% of the interviewed allergists offered POIT in clinical studies or used self-developed approaches. Results: The physicians consistently reported conducting food challenges in 5-10% of patients to confirm a peanut allergy diagnosis. The allergists who offered POIT described using a variety of approaches. Areas of divergence included patient selection (ages, 4-7 years), peanut material (crushed peanuts, peanut flour, peanut protein, peanut butter, peanut extract), starting and ending doses, and updosing intervals (1 to 2 weeks). Generally, POIT administration and observation occupied an examination room for up to 2 hours; some practices reported accommodating 2 to 5 patients who received POIT simultaneously. Among physicians who did not offer POIT, barriers included medicolegal risks and the lack of a U.S. Food and Drug Administration (FDA) approved therapy. Conclusion: Although POIT is currently not supported in treatment guidelines, some allergists have developed experimental POIT approaches to support patient needs. In the absence of a product that has approval by the FDA, European Medicines Agency (EMA) or other national competent authority, substantial variability in POIT approaches exists. Although logistical factors are not major obstacles to adoption, POIT dose preparation can be perceived as burdensome, and observation requires a dedicated staff. All the physicians interviewed suggested a need for effective, FDA-approved, disease-modifying treatments.