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The study aimed to identify predictors of severe acute hypertension (≥180/110 mmHg) during severe hypoglycemia and to assess the efficacy of prior use of catecholamine-blocking agents for preventing adverse influences in diabetic patients with severe hypoglycemia. We performed a retrospective study between January 2006 and March 2012 to assess diabetic patients with severe hypoglycemia at a single center in Japan. Severe hypoglycemia was defined as the presence of any hypoglycemic symptoms that required the medical assistance of another person after visiting the emergency room by ambulance. Multivariate logistic regression analysis was performed to identify possible predictors of severe hypertension due to severe hypoglycemia and to assess whether prior use of alpha- or beta-blockers is beneficial for the prevention of severe hypertension in diabetic patients with severe hypoglycemia. Multivariate adjustments were made for age, sex, preexisting hypertension, history of ischemic heart disease, blood glucose level upon arrival, estimated GFR, and prior use of alpha- or beta-blockers. A total of 59,602 patients who visited the emergency room were screened and 352 diabetic patients with severe hypoglycemia were enrolled. Incidences of severe hypertension before and at 3 and 6 hours after the initiation of antihypoglycemic treatment were 21.3%, 6.7%, and 0% in patients with type 1 diabetes (n = 61) and 38.8%, 18.2%, and 8.2% in patients with type 2 diabetes (n = 291), respectively. Aging was positively (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00−1.03; P = 0.02) and female sex was negatively (OR, 0.50; 95% CI, 0.29−0.86; P = 0.01) associated with occurrence of severe hypertension during severe hypoglycemia. In addition, prior use of beta-blockers was negatively associated with occurrence of severe hypertension during severe hypoglycemia using multivariate logistic regression analysis (OR, 0.31; 95% CI, 0.11−0.83; P = 0.02). None of the patients with prior use of beta-blockers had hypokalemia (<3.0 mEq/L). Prior use of beta-blockers may prevent adverse influences such as severe hypertension and hypokalemia during severe hypoglycemia in diabetic patients.