The current treatments for irritable bowel syndrome (IBS) are suboptimal. The findings of previous studies of rifaximin treatment for IBS may have differed due to variations in study design. Our study aimed to determine the therapeutic and adverse effects of rifaximin treatment for IBS based on a meta-analysis of published randomized controlled trials (RCTs). We searched the MEDLINE, EMBASE, EBSCO, Springer, Ovid, and Cochrane Library databases for RCTs investigating the effects of rifaximin on IBS. Data from each selected RCT was evaluated individually based on an intention-to-treat analysis, and a meta-analysis was performed in which the odds ratios (ORs) and 95% confidence intervals (CIs) of clinical outcomes and adverse events were calculated using fixed-effects models. Four eligible studies were identified. Overall relief of IBS symptoms in the rifaximin groups was greater than that in the placebo groups at the ends of both the treatment and follow-up periods (OR = 1.19; 95% CI: 1.08-1.32 and OR = 1.36; 95% CI: 1.18-1.58, respectively, P < 0.05 for both). Significant relief of abdominal distention was observed at the follow-up endpoint (OR = 1.69; 95% Cl: 1.27-2.23; P < 0.05), but not at the treatment endpoint (OR = 1.19; 95% CI: 0.96-1.49; P > 0.05). Abdominal pain (OR = 1.01; 95% CI: 0.98-1.03; P > 0.05), nausea (OR = 1.00; 95% CI: 0.98-1.02; P > 0.05), vomiting (OR: 0.99; 95% CI: 0.98-1.01; P > 0.05), and headache (OR = 1.01; 95% CI: 0.98-1.03; P > 0.05) did not differ significantly between the rifaximin and placebo groups. In the RCTs selected, our meta-analysis showed that the efficacy of rifaximin for the resolution of overall IBS symptoms was greater than that of the placebos, and that rifaximin was well-tolerated. The course of relief from abdominal distention in IBS patients treated with rifaximin may be delayed in some patients, compared with that of overall IBS symptom relief.