BACKGROUND: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated. METHODS: Adolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed(R) 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase. RESULTS: Adolescents (mean +/- standard deviation [SD] 16.5 +/- 2.29 years of age and 7.7 +/- 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%-88.4%) of the time (2977 patient-days). Adults (mean +/- SD 44.6 +/- 12.79 years of age and 26.4 +/- 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% +/- 0.8% to 7.1% +/- 0.6% (P < 0.001) and from 7.3% +/- 0.9% to 6.8% +/- 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% +/- 10.9% to 67.2% +/- 8.2% (P < 0.001) in adolescents and from 68.8% +/- 11.9% to 73.8% +/- 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT(R) blood glucose values was 67.4% +/- 27.7% compared to SG values of 72.0% +/- 11.6% for adolescents and 74.2% +/- 17.5% compared to 76.9% +/- 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort. CONCLUSIONS: HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA1c, hyperglycemia and hypoglycemia, compared to baseline. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02463097.