To assess the repeatability in human volunteers of software-quantified small bowel motility captured with magnetic resonance (MR) imaging and to test the ability to detect changes in motility induced by pharmacologic agents. The study was approved by the Royal Free Research Ethics Committee, and all subjects gave full written informed consent. Twenty-one healthy volunteers (14 men, seven women; mean age, 28 years) underwent cine MR imaging with a three-dimensional balanced turbo field-echo sequence to capture small bowel motility. Volume blocks (15 cm thick) were acquired every second during a 20-second breath hold. A randomized, blinded, placebo-controlled crossover study of either 0.5 mg neostigmine or saline (n = 11) or 20 mg intravenous butylscopolamine or saline (n = 10) was performed with motility MR imaging at baseline and repeated at a mean of 4 weeks (range, 2-7 weeks). Two readers independently drew regions of interest around the small bowel, and motility was quantified by using a registration algorithm that provided a global motility metric in arbitrary units. Repeatability of the motility measurements at baseline was assessed by using Bland-Altman and within-subject coefficient of variation measures. Changes in mean motility measurements after drug administration were compared with those after placebo administration by using paired t testing. The repeatability between baseline measurements of motility was high; the Bland-Altman mean difference was -0.0025 (range, 0.28-0.4), the 95% limit of agreement was ±0.044 arbitrary units (au), and the within-subject coefficient of variation was 4.9%. Measured motility with neostigmine (mean, 0.39 au) was significantly higher than that with placebo (mean, 0.34 au; P < .001), whereas that with butylscopolamine (mean, 0.13 au) was significantly lower than that with placebo (mean, 0.30 au; P < .001). Quantification of small bowel motility with use of MR imaging in healthy volunteers is repeatable and sensitive to changes induced by means of pharmacologic manipulation. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130151/-/DC1.