Background/Aims: Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD. Methods: Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used. Results: One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70–0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 μg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity. Conclusions FC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.