Background and Aims: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury. The aim of this investigator-initiated FITCH trial (Fibrates for cholestatic ITCH) was to assess effects of bezafibrate on pruritus in patients with PSC, PBC, and SSC. Methods: Patients with moderate to severe pruritus (≥5 of 10 on visual analog scale [VAS]) due to PSC, PBC, or SSC were recruited for this double-blind, randomized, placebo-controlled trial between 2016 and 2019. Patients received once-daily bezafibrate (400 mg) or placebo for 21 days. The primary end point was ≥50% reduction of pruritus (VAS; intention-to-treat). Results: Of 74 randomized patients, 70 completed the trial (95%; 44 PSC, 24 PBC, 2 SSC). For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to ≥50% reduction of severe or moderate pruritus (P =.003). For secondary end points, bezafibrate reduced morning (P =.01 vs placebo) and evening (P =.007) intensity of pruritus (VAS) and improved the validated 5D-Itch questionnaire (P =.002 vs placebo). Bezafibrate also reduced serum alkaline phosphatase (−35%, P =.03 vs placebo) correlating with improved pruritus (VAS, P =.01) suggesting reduced biliary damage. Serum bile acids and autotaxin activity remained unchanged. Serum creatinine levels tended to mildly increase (3% bezafibrate, 5% placebo, P =.14). Conclusions: Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. Trial Registration: Netherlands Trial Register, ID: NTR5436 (August 3, 2015), ClinicalTrials.gov ID: NCT02701166 (March 2, 2016).