OBJECTIVE: To look for technical simplification and economic efficiency in the treatment of pediatric diabetic ketoacidosis (DKA) with subcutaneous use of the fast-acting insulin analog (lispro) and compare its use with regular intravenous insulin treatment. RESEARCH DESIGN AND METHODS: In this controlled clinical trial from June 2001 to June 2003, we randomized 60 episodes of DKA with a blood glucose level > or = 16.6 mmol/l (300 mg/dl), venous pH <7.3 and/or bicarbonate <15 mmol/l, or ketonuria greater than + +. Of the 60 episodes, 30 were treated with subcutaneous lispro (0.15 units/kg) given every 2 h (lispro group) and the other 30 cases received continuous intravenous regular insulin (0.1 unit x kg(-1) x h(-1); CIRI group). Volume deficit was repaired with 10-ml/kg aliquots of 0.9% sodium chloride. Laboratory monitoring included hourly bedside capillary glucose, venous blood gas, beta-hydroxybutyrate, and electrolytes. Plasma blood glucose levels were measured on admission, 2 h after admission, when capillary blood glucose reached < or = 13.8 mmol/l (250 mg/dl), and 6, 12, and 24 h thereafter. RESULTS: Capillary glucose levels decreased by 2.9 and 2.6 mmol x l(-1) x h(-1) in the lispro and CIRI groups, respectively, but blood glucose fluctuated at different time intervals. In the CIRI group, metabolic acidosis and ketosis resolved in the first 6-h period after capillary glucose reached 13.8 mmol/l, whereas in the lispro group, they resolved in the next 6-h interval; however, both groups met DKA recovery criteria without complications. CONCLUSIONS: DKA treatment with a subcutaneous fast-acting insulin analog represents a cost-effective and technically simplified procedure that precludes intensive care unit admission.