OBJECTIVE We aimed to assess the feasibility and safety of hybrid closed-loop insulin delivery in children with type 1 diabetes aged 1–7 years as well as evaluate the role of diluted insulin on glucose control. RESEARCH DESIGN AND METHODS In an open-label, multicenter, multinational, randomized crossover study, 24 children with type 1 diabetes on insulin pump therapy (median age 5 years [interquartile range 3–6] and mean ± SD HbA1c 7.4 ± 0.7% [57 ± 8 mmol/mol] and total insulin 13.2 ± 4.8 units/day) underwent two 21-day periods of unrestricted living and we compared hybrid closed-loop with diluted insulin (U20) and hybrid closed-loop with standard strength insulin (U100) in random order. During both interventions, the Cambridge model predictive control algorithm was used. RESULTS The proportion of time that sensor glucose was in the target range between 3.9 and 10 mmol/L (primary end point) was not different between interventions (mean ± SD 72 ± 8% vs. 70 ± 7% for closed-loop with diluted insulin vs. closed-loop with standard insulin, respectively; P = 0.16). There was no difference in mean glucose levels (8.0 ± 0.8 vs. 8.2 ± 0.6 mmol/L; P = 0.14), glucose variability (SD of sensor glucose 3.1 ± 0.5 vs. 3.2 ± 0.4 mmol/L; P = 0.16), or the proportion of time spent with sensor glucose <3.9 mmol/L (4.5 ± 1.7% vs. 4.7 ± 1.4%; P = 0.47) or <2.8 mmol/L (0.6 ± 0.5% vs. 0.6 ± 0.4%; P > 0.99). Total daily insulin delivery did not differ (17.3 ± 5.6 vs. 18.9 ± 6.9 units/day; P = 0.07). No closed-loop–related severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS Unrestricted home use of day-and-night closed-loop in very young children with type 1 diabetes is feasible and safe. The use of diluted insulin during closed-loop does not provide additional benefits compared with standard strength insulin.