BACKGROUND: Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied. OBJECTIVE: To determine the relation between TN sensitization levels and OFC outcomes. METHODS: Open TN OFCs performed from 2007 through 2015 at a referral center were analyzed to compare outcome based on skin prick test (SPT) wheal size, food-specific immunoglobulin E (sIgE), peanut co-allergy, and TN sensitization only vs TN allergy with sensitization to other TNs. Delayed OFC was defined as longer than 12 months from the time of an sIgE level lower than 2 kUA/L. RESULTS: Overall passage rate was 86% for 156 TN OFCs in 109 patients (54 almond, 28 cashew, 27 walnut, 18 hazelnut, 14 pecan, 13 pistachio, and 2 Brazil nut). Passage rates were 76% (n = 67) in patients with a history of TN allergy who were challenged to another TN to which they were sensitized and 91% (n = 65) in those with TN sensitization only (mean sIgE 1.53 kUA/L; range 0.35-9.14). Passage rates were 89% (n = 110 of 124) for a TN sIgE level lower than 2 kUA/L and 69% (11 of 16) for a TN sIgE level of at least 2 kUA/L. In 44 challenges in patients with peanut allergy and TN co-sensitization, the TN OFC passage rate was 96%. In 41 TN OFCs with a TN SPT wheal size of at least 3 mm, 61% passed, with a mean wheal size of 4.8 mm (range 3-11) in those passing vs 9 mm (range 3-20) in those failing. CONCLUSION: TN challenges are frequently passed in patients with TN sensitization with or without a history of TN reactivity despite a TN SPT wheal of at least 3 mm or a TN sIgE level of at least 2 kUA/L. Nearly all patients with peanut allergy and TN co-sensitization passed the TN challenge, questioning the clinical relevance of "co-allergy."