Dai et al provided comments on the use of the nonsystemic antibiotic rifaximin for diarrhea-predominant irritable bowel syndrome (IBS-D) and data from the TARGET 3 repeat treatment trial of rifaximin for adults with IBS-D.1 Specifically, concerns were voiced regarding the percentage improvement over placebo reported in the TARGET 3 trial.1 However, it is important to note that TARGET 3 was not a primary efficacy trial. Two randomized, double-blind, placebo-controlled, phase III trials (TARGET 1 and 2) previously demonstrated the efficacy of rifaximin over placebo.