Background <p>Fibrofatty proliferation of mesenteric fat is a common finding on magnetic resonance enterography (MRE) in Crohn’s disease (CD) patients. Mesenteric fat may play a role in inflammation, fibrosis, and stricture formation, but its prognostic value in predicting complications remains unclear.</p> Objectives <p>To assess the association between mesenteric fat proliferation on MRE and the risk of hospital admissions and bowel surgery in CD patients.</p> Methods <p>In this retrospective single-center study, CD patients with available MRE data were followed for CD exacerbation-related hospitalizations or abdominal surgeries. An expert radiologist reviewed MRE for intestinal wall thickening, stricture, abscess formation, fibrofatty proliferation, and fat edema. Kaplan-Meier and Cox proportional hazards regression models were used to analyze associations between mesenteric fat and outcomes, adjusting for clinical and imaging characteristics.</p> Results <p>Among 175 CD patients mesenteric fat proliferation and edema were noted in 52 (29.7%) and 15 (8.9%) patients, respectively. Other findings included wall thickening (46.9% mild, 29.1% moderate, 7.4% severe), stricture (14.3%), abscess (5.7%), and fistula (6.9%). During a mean follow-up of 95.2 months, 93 (51.3%) patients were hospitalized for CD-related reasons, and 47 (26.9%) underwent CD-related abdominal surgery. Mesenteric fat proliferation was strongly associated with hospitalizations and surgery (<i>p</i> &lt; 0.0001 for both). Multivariable analysis confirmed these associations with adjusted hazard ratios (aHR) of 3.45 (95%CI 1.66–7.19) 3.74 (95%CI) for surgery and 1.92 (95%CI 1.16–3.15) 2.03 (95%CI) for hospitalizations. Fat edema was linked to surgery and hospitalization but lost significance in multivariable analysis.</p> Conclusions <p>Mesenteric fat proliferation on MRE is independently associated with increased risk of hospitalizations and surgery in CD patients.</p>