Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD. Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591. Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1–2 h across Days 1, 5 and 10. Cmax ranges were 1.2–154 ng/mL for fidaxomicin and 4.7–555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8–2170 μg/g for fidaxomicin and 0–1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death. Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.