OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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 <or=13 years, and duration of diabetes was 4.4 years (range 1.0-9.4). RESULTS: 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 micro mol/l; postprandial 383 +/- 83 vs. 385 +/- 77 micro mol/l) and HbA(1c) (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. CONCLUSIONS: 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.