Non-inferiority (NI) trials are becoming increasingly popular. The main purpose of NI trials is to assert the efficacy of a new treatment compared with an active control by demonstrating that the new treatment maintains a substantial fraction of the treatment effect of the control. Most of the statistical testing procedures in this area have been developed for three-arm NI trials in which a new treatment is compared with an active control in the presence of a placebo. However, NI trials frequently involve comparisons of several new treatments with a control, such as in studies involving different doses of a new drug or different combinations of several new drugs. In seeking an adequate testing procedure for such cases, we use a new approach that modifies existing testing procedures to cover circumstances in which several new treatments are present. We also give methods and algorithms to produce the optimal sample size configuration. In addition, we also discuss the advantages of using different margins for the assay sensitivity test between the active control and the placebo and the NI test between the new treatments and the active control. We illustrate the new approach by using data from a clinical trial. Copyright © 2012 John Wiley & Sons, Ltd.