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The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 diabetes.Forty-two children (aged 6-12 years) and 34 adolescents (13-17 years) were randomized to preprandial (immediately before meal start) and postprandial (immediately after a meal or a maximum of 30 min after meal start) treatment with insulin aspart (at least thrice daily) as part of a basal/bolus regimen in a multicenter study with an open labeled, two-period cross-over design (6-week periods). Of this group, 49% were boys, 55% were aged ≤13 years, and duration of diabetes was 4.4 years (range 1.0-9.4).Glycemic control for postprandial treatment was not worse than preprandial treatment as assessed by fructosamine week 0 vs. 6 (mean ± SD, preprandial 367 ± 74 vs. 378 ± 90 μmol/l; postprandial 383 ± 83 vs. 385 ± 77 μmol/l) and HbA1c (preprandial 7.9 ± 1.3 vs. 8.0 ± 1.5%; postprandial 8.0 ± 1.4 vs. 8.3 ± 1.5%, P = 0.14). The only statistically significant finding from the seven-point blood glucose profiles and derived parameters between preprandial and postprandial treatment was a lower postprandial glucose level 120 min after breakfast (mean ± SEM, −2.08 ± 0.74 mmol/l, P = 0.016). The relative risk of hypoglycemia (blood glucose <3.9 mmol/l) preprandially to postprandially was not significantly different (mean 1.1; 95% CI 0.91-1.35; P = 0.31). Overall treatment satisfaction was equally high for both regimens with both patients and parents.Although preprandial administration of insulin aspart is generally preferable, this study shows that in children and adolescents, postprandial administration of insulin aspart is a safe and effective alternative.