Background. Hypoglycemia due to inadequate carbohydrate intake is a frequent complication of insulin treatment of diabetic in-patients. Objective. To assess the effectiveness of a nurse-managed protocol to prevent hypoglycemia during subcutaneous insulin treatment. Design. Prospective pre-post-intervention study. Methods. In 350 consecutive diabetic in-patients the incidence of hypoglycemia (blood glucose < 70 mg/dL) during subcutaneous insulin treatment was assessed before (phase A) and after (phase B) the protocol was adopted to permit (1) the patient to opt for substitutive food to integrate incomplete carbohydrate intake in the meal; (2) in case of lack of appetite or repeatedly partial intake of the planned food, prandial insulin administered at the end of the meal to be related to the actual amount of carbohydrates eaten; (3) intravenous infusion of glucose during prolonged fasting. Results. Eighty-four patients in phase A and 266 in phase B received subcutaneous insulin for median periods of, respectively, 7 (Q1–Q3 6–12) and 6 days (Q1–Q3 4–9). Hypoglycemic events declined significantly from 0.34 ± 0.33 per day in phase A to 0.19 ± 0.30 in phase B (P>0.001). Conclusions. A nurse-managed protocol focusing on carbohydrate intake reduced the incidence of hypoglycemia in patients with diabetes receiving subcutaneous insulin in hospital.