Background/aims The Lewis Score (LS) can assess inflammatory activity on small bowel capsule endoscopy (SBCE). We aimed to evaluate the LS usefulness in the setting of suspected Crohn's Disease (CD). Methods Retrospective single-center study including 56 patients undergoing SBCE for suspected CD. Patients were divided into three groups, according to clinical presentation: Group 1 (28 patients): suspected CD not supported by the International Conference on Capsule Endoscopy (ICCE) criteria; Group 2 (19 patients): suspected CD based on two ICCE criteria; Group 3 (9 patients): patients fulfilling three or more criteria. Inflammatory activity was assessed with the LS. The diagnosis of CD required a minimum follow-up of 6months after SBCE, basing on clinical evaluation, endoscopic, histological, radiological, and/or biochemical investigations. Results SBCE detected significant inflammatory activity (LS≥135) in 23 patients (41.1%), being 5 patients from Group 1 (17.8%), 11 from Group 2 (57.9%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 23 patients (41.1%): six patients from Group 1 (21.4%), 10 from Group 2 (52.6%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 82.6% of patients with significant inflammatory activity on CE (LS≥135), but in only 12.1% of those having a LS<135 (p<0.05). The LS Positive Predictive Value, Negative Predictive Value, Sensitivity and Specificity were 82.6%, 87.9%, 82.6% and 87.9%, respectively. Conclusions The LS may be a valuable diagnostic tool in the setting of suspected CD. Patients not fulfilling the ICCE criteria have lower LS and fewer are diagnosed with CD during follow-up.