Forty-three patients with irritable bowel syndrome (IBS) according to Rome II criteria were randomly assigned to receive either acupuncture (AC, n = 22) or sham acupuncture (SAC, n = 21) using the so-called ‘Streitberger needle’. Treatment duration was 10 sessions with an average of two acupuncture sessions per week, and the primary endpoint was improvement in quality of life (QoL) using the Functional Digestive Diseases Quality of Life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared to baseline assessment. QoL measurement was repeated 3 months after treatment. Both the AC and SAC groups improved significantly in global QoL by the FDDQL at the end of treatment (P = 0.022), with no differences between the groups. The SF-36 was insensitive to these changes (except for pain). This effect was partially reversed 3 months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) in a stepwise regression model. Acupuncture in IBS is primarily a placebo response. Based on the small differences found between AC and SAC, a study including 566 patients would be necessary to prove efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.