Over half of patients with irritable bowel syndrome have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licensed pharmacological therapies in IBS-D and IBS-M is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty. We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane central register of controlled trials, and clinicaltrials.gov through November 2018 to identify randomised controlled trials (RCTs) assessing the efficacy of licensed pharmacological therapies in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk of remaining symptomatic with 95% confidence intervals (CIs) to summarise the effect of each comparison tested. Treatments were ranked according to their P-score. We identified 18 eligible RCTs (7 alosetron, 5 ramosetron, 2 rifaximin, 4 eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS (Figure 1). Alosetron 1mg twice-daily ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency (RR = 0.69; 95% CI 0.60 to 0.80, P-score = 0.97), effect on global symptoms of IBS, and effect on stool consistency. Ramosetron 2.5mcg once-daily was ranked first for effect on abdominal pain (RR = 0.75; 95% CI 0.65 to 0.85, P-score = 0.94). Total numbers of adverse events were significantly greater with alosetron 1mg twice-daily and ramosetron 2.5mcg, once-daily, compared with placebo. Rifaximin 550mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550mg three times daily. In a network meta-analysis of randomised controlled trials of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective. Abstract PWE-076 Figure 1. Forest Plot of the Indirect Evidence for Failure to Achieve the FDA-recommended Endpoint to Define Treatment Response.