Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS–Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.