Purpose To assess whether contrast material-enhanced ultrasonography (US) can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease after 6 weeks of pharmacologic treatment. Materials and Methods This prospective study was approved by our ethics committee, and written informed consent was obtained from all patients. Fifty consecutive patients (26 men and 24 women; mean age, 34.76 years ± 9) with a proved diagnosis of active Crohn disease who were scheduled to begin therapy with biologics (infliximab or adalimumab) were included, with enrollment from June 1, 2013, to June 1, 2015. In each patient, the terminal ileal loop was imaged with contrast-enhanced US before the beginning and at the end of week 6 of pharmacologic treatment. Time-intensity curves obtained in responders (those with a decrease in the Crohn disease endoscopic index of severity score of 25-44 before treatment to 10-15 after treatment, an inflammatory score <7, and/or a decrease ≥70 in the Crohn disease activity index score compared with baseline) and nonresponders were compared with Mann-Whitney test. Results Responders (n = 31) and nonresponders (n = 19) differed (P < .05) in the percent change of peak enhancement (-40.78 ± 62.85 vs 53.21 ± 72.5; P = .0001), wash-in (-34.8 ± 67.72 vs 89.44 ± 145.32; P = .001) and washout (-5.64 ± 130.71 vs 166.83 ± 204.44; P = .002) rate, wash-in perfusion index (-42.29 ± 59.21 vs 50.96 ± 71.13; P = .001), area under the time-intensity curve (AUC; -46.17 ± 48.42 vs 41.78 ± 87.64; P = .001), AUC during wash-in (-43.93 ± 54.29 vs 39.79 ± 70.85; P = .001), and AUC during washout (-49.36 ± 47.42 vs 42.65 ± 97.09; P = .001). Responders and nonresponders did not differ in the percent change of rise time (5.09 ± 49.13 vs 6.24 ± 48.06; P = .93) and time to peak enhancement (8.82 ± 54.5 vs 10.21 ± 43.25; P = .3). Conclusion Analysis of time-intensity curves obtained after injection of microbubble contrast material 6 weeks after beginning pharmacologic treatment can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease. 