['Early diagnosis of dysplastic changes and exclusion of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) remain a major clinical challenge. Although SpyGlass single-operator cholangioscopy (SOC) appears effective in diagnostics of indeterminate biliary strictures, there are only few studies on its safety in PSC-related strictures.', 'The aim of this study was to assess the clinical feasibility of SOC and directed biopsies, flow cytometry, and brush cytology in PSC patients.', 'Eleven consecutive patients (median age 45 years, 5 females) undergoing SOC for progression of PSC in a single tertiary center were included in a prospective observational study.', 'Brush sample and directed biopsies were successfully acquired from strictures in all cases. Samples were adequate for cytological and histological diagnosis in 9 (82%) and 10 patients (91%), respectively. There were two cases of pancreatitis. In one patient, flow cytometry showed aneuploidy, which resulted in closer follow-up.'] Does spyglass single-operator peroral cholangioscopy seem promising in the evaluation of primary sclerosing cholangitis-related biliary strictures?