Background: Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn's disease (CD) are still limited. Aim: To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods: Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (!3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results: Of 114 included patients, 107 (94%) had failed ! 1 and 58 (51%) ! 2 biological agents (antitumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N ¼ 65) decreased from 6 to 4 mg/l (p ¼ .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions: In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option.