OBJECTIVE: Crohn's disease (CD) is heterogeneous, and proximal involvement in the small bowel (SB) is associated with worse outcomes. Nonetheless, studies on the impact of duodenal and jejunal lesions in SB CD are limited. This study aimed to investigate the clinical characteristics and outcomes of individuals diagnosed with SB CD, comparing those with and without proximal inflammation. METHODS: A cohort of 53 treatment-naive SB CD patients that underwent Capsule Endoscopy at diagnosis were retrospectively selected. The inflammatory activity was quantified using the Lewis Score for each SB tertile. RESULTS: Thirty-seven (69.8%) patients displayed inflammatory activity in the first and/or second tertile together with third tertile involvement (Proximal+T3 group). Sixteen (30.2%) had inflammation in the third tertile only (T3 group). Individuals in the Proximal+T3 group had a higher risk for moderate-to-severe inflammation (OR 4.93, 95% CI: 1.3-18.3, p=0.013). A subgroup analysis for those with mild inflammatory activity showed that individuals in the Proximal+T3 group initiated biologic drugs more often (OR 11, 95% CI: 1.1-109.7, p=0.036). CONCLUSION: Proximal SB lesions are associated with increased inflammatory activity, necessitating more frequent use of biologics in patients with mild disease. Early detection of proximal SB CD with Capsule Endoscopy may contribute to timely treatment.