Acute caffeine (CAF) ingestion impairs glucose tolerance in able-bodied humans during an oral glucose tolerance test (OGTT). The mechanism responsible for this effect remains unclear however it is suggested to be due to the accompanying increase in epinephrine concentration [EPI]. We examined whether or not CAF would elicit a glucose intolerance in persons with tetraplegia (TP) who do not exhibit an increased EPI response following CAF ingestion. All TP [n = 14; 9 incomplete (INC) lesion, 5 complete (COM) lesion] completed 2 OGTT 1 h after consuming either gelatin (PL) or CAF capsules (dose = 4 mg/kg). Blood samples were collected at baseline (t = 0 min), 1 h post capsule ingestion (t = 60 min) and every 30 min during the OGTT (t = 90 to 180 min). Glucose, insulin, proinsulin and C peptide responses were similar (P > 0.05) between treatments demonstrating no effect of CAF on glucose tolerance. This lack of a CAF effect may be due to the low [EPI] that remained unchanged (P > 0.05) throughout all experiments. Interestingly, the COM exhibited a 50% higher glucose response (P 0.05) and a 46% (P > 0.05) lower insulin response (vs. INC) suggesting a more pronounced glucose intolerance within this subgroup. Furthermore, 9 TP (5 COM, 4 INC) had glucose levels of 7.8 mM at the end of the OGTT (t = 180 min), classifying them as glucose intolerant. In summary, acute CAF ingestion does not increase [EPI] nor impair glucose tolerance in TP.