Introduction: The HR and BP responses to exercise (exercise pressor reflex, EPR) predict adverse clinical events in patients with Heart Failure (HF). Although studies have shown that hyperglycemia may induce cardiovascular autonomic dysregulation, the association between glycemic status and EPR in HF patients is poorly understood. Hypothesis: Hyperglycemia would be accompanied by altered EPR after the 6-minute walk test (6MWT) in nondiabetic HF patients. Methods: The HR and BP (SBP and DBP) responses to 6MWT were evaluated in 215 HF ambulatory patients aged 62.4 ± 9.4 (M ± SD) years old before (BASE), immediately after (P0), 1 minute after (P1) and 3 minutes after exercise (P3). Patients were assigned to one of two groups based on their 2-hours post meal (breakfast) glycemia into normoglycemic (<140mg/dl; NG; n = 173) and hyperglycemic (HG; n =42). Results: To compare the HR and BP responses to the 6MWT between the groups a 4 X 2 ([BASE X P0 X P1 X P3] X [NG x HG]) repeated measures analysis of covariance using least significant difference as alpha adjustment that controlled for weight and gender were conducted. Significant (P<0.05) time-by-group interactions occurred for HR, SBP, and DBP such that HR at P0, SBP at BASE, P1 and P3 and DBP at P1 and P3 were higher in the HG group compared to the NG. In addition, we found that SBP response to exercise was blunted where as DBP remained elevated at P1 and P3 in HG group only (see Figure 1). Conclusions: These results demonstrate that post-meal hyperglycemia evokes an abnormal EPR in patients with HF. Such effects might be caused by a hyperglycemia-induced impaired autonomic dysregulation. Future attention should be given at the patient’s glycemic status prior to using an exercise test as it significantly contributes to the EPR.