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Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes. [ABSTRACT FROM AUTHOR]