Background: Acupuncture has traditionally been used in the treatment of inflammatory bowel disease in China and is increasingly being applied in Western countries. The purpose of this study was to investigate the efficacy of acupuncture in the treatment of active Crohn’s disease (CD). Methods: A prospective, randomized, controlled, single-blind clinical trial was carried out to analyze the change in the CD activity index (CDAI) after treatment as a main outcome measure, and the changes in quality of life and general well-being, serum markers of inflammation (α1-acid glycoprotein, C-reactive protein) as secondary outcome measures. 51 patients with mild to moderately active CD were treated in a single center for complementary medicine by three trained acupuncturists and randomly assigned to receive either traditional acupuncture (TCM group, n = 27) or control treatment at non-acupuncture points (control group, n = 24). Patients were treated in 10 sessions over a period of 4 weeks and followed up for 12 weeks. Results: In the TCM group the CDAI decreased from 250 ± 51 to 163 ± 56 points as compared with a mean decrease from 220 ± 42 to 181 ± 46 points in the control group (TCM vs. control group: p = 0.003). In both groups these changes were associated with improvements in general well-being and quality of life. With regard to general well-being, traditional acupuncture was superior to control treatment (p = 0.045). α1-acid glycoprotein concentration fell significantly only in the TCM group (p = 0.046). Conclusions: Apart from a marked placebo effect, traditional acupuncture offers an additional therapeutic benefit in patients with mild to moderately active CD.