BACKGROUND: In inflammatory bowel disease (IBD), a flare can be due to natural history of disease or due to gastrointestinal infection. Infection is conventionally diagnosed by stool microscopy and culture. Stool multiplex polymerase chain reaction (PCR) assay or Biofire(R) FilmArray((R)) GI Panel is a sensitive and rapid test for detecting infection, but is expensive; its impact on management and cost-effectiveness has not been studied in IBD. AIMS: To compare stool PCR assay and conventional tests during IBD flare for detection of infection, impact of detection on treatment and cost-effectiveness of the tests. METHODS: Sixty-five patients with IBD flare underwent conventional stool tests (microscopy, culture and Clostridioides difficile toxin assay) and stool PCR assay simultaneously. RESULTS: We prospectively enrolled 65 consecutive patients presenting with disease flare: ulcerative colitis (58 patients, 28 women, mean age 41.1 years) and Crohn's disease (seven patients; three women; mean age 36.1). Stool PCR detected organisms in 36 (55.4%) patients as compared to six (9.2%) by conventional tests (p < 0.0001). The organisms detected by the PCR assay were enteroaggregative (EAEC) (22 patients), enteropathogenic (EPEC) (12), enterotoxigenic Escherichia coli (ETEC) (5), Plesiomonas shigelloides (4), C. difficile (3), norovirus (3), enteroinvasive E. coli (2), rotavirus (2) and G. lamblia, cryptosporidia, cyclospora, Sapovirus, adenovirus and Entamoeba histolytica (one each). PCR organism detection resulted in management change in 13 (20%) patients as compared to five (7.6%) by conventional tests (p < 0.02). Cost to achieve one positive result on stool PCR that led to management change was INR 60,000 (USD 690, EUR 638) as compared to Indian Rupees (INR) 54,600 (United States Dollar [USD] 627, EUR 580) for conventional tests. The incremental cost-effective ratio (ICER) was INR 63,375 (USD 728, EUR 674). CONCLUSION: In an IBD flare, stool PCR or Biofire(R) FilmArray((R)) GI Panel detected more organisms and led to more frequent management change as compared to conventional tests. The ICER was INR 63,375 (USD 728, EUR 674). This test should be considered first-line investigation in an IBD flare.