OBJECTIVE: Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) and multiple daily injections (MDIs) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospectively compared in people naïve to either regimen in a multicenter study. We aimed to help close that deficiency. RESEARCH DESIGN AND METHODS: People with type 1 diabetes on NPH-based insulin therapy were randomized to CSII or glargine-based MDI (both otherwise using lispro) and followed for 24 weeks in an equivalence design. Fifty people were correctly randomized, and 43 completed the study. RESULTS: Total insulin requirement (mean +/- SD) at end point was 36.2 +/- 11.5 units/day on CSII and 42.6 +/- 15.5 units/day on MDI. Mean A1C fell similarly in the two groups (CSII -0.7 +/- 0.7%; MDI -0.6 +/- 0.8%) with a baseline-adjusted difference of -0.1% (95% CI -0.5 to 0.3). Similarly, fasting blood glucose and other preprandial, postprandial, and nighttime self-monitored plasma glucose levels did not differ between the regimens, nor did measures of plasma glucose variability. On CSII, 1,152 hypoglycemia events were recorded by 23 of 28 participants (82%) and 1,022 in the MDI group by 27 of 29 patients (93%) (all hypoglycemia differences were nonsignificant). Treatment satisfaction score increased more with CSII; however, the change in score was similar for the groups. Costs were approximately 3.9 times higher for CSII. CONCLUSIONS: In unselected people with type 1 diabetes naïve to CSII or insulin glargine, glycemic control is no better with the more expensive CSII therapy compared with glargine-based MDI therapy.