Aim of the study was to test the reproducibility of estimates of static, Phi s, and dynamic, Phi d, beta-cell sensitivity to glucose, and predictions of the insulin secretion rate, SR(t), provided by the C-peptide oral minimal model (COMM) applied to oral glucose tolerance tests (OGTT) of various complexity. The study involved six volunteer, normotensive and normoglycemic subjects who underwent a 300-minute OGTT. Results from a full 22-sampling schedule (OGTT300/22), were compared with those from two reduced schedules consisting of 11 samples in 300 min (OGTT300/11) and 7 samples in 120 min (OGTT120/7). Our results showed that both reduced-sample protocols did not affect significantly the estimates of Phi d. Intraclass correlation coefficients were higher than 0.9. The Phi s appeared more sensitive to reductions of protocol complexity. Nevertheless, intraclass correlation coefficients kept higher than 0.7. No significant differences were found in model predictions of SR(t) profiles among all tested OGTT protocols. These findings confirm the COMM as a potentially useful tool to quantify beta-cell sensitivity and insulin secretion rate in pathophysiological studies, from relatively low-cost OGTT.