Abstract Aim This study aims to assess the health‐related quality of life (HRQoL) in a Dutch population of patients with primary biliary cholangitis (PBC) in relation to the prognosis and need for second line‐therapy, based on both objective disease parameters and patients’ perspectives. Methods In this cross‐sectional multicenter study, HRQoL was assessed by using the Dutch PBC‐40 according to objective clinical parameters and patients’ perspectives on treatment and prognosis. Results In total, 178/269 (66%) patients responded; mean age 61.2 (SD 9.9) years and 165 (92.7%) women. The PBC‐40 domain scores did not differ according to the GLOBE score response ( p > 0.05 for all) or according to the POISE criteria ( p > 0.05), except for the domain itch ( p = 0.031). Patients who considered their survival to be impaired scored higher on all domains as compared to those expecting a normal prognosis ( p < 0.05). Similarly, PBC‐40 domain scores were higher among patients who considered that they were in need of additional therapy compared to those who did not ( p < 0.05 for all, except for domain itch [ p = 0.056]). However, 45/62 (72.6%) patients with a self‐expected impaired prognosis had a GLOBE score indicative of a normal prognosis. Twenty‐five of the 40 (62.5%) patients who believed they needed additional therapy were below POISE criteria. Conclusion The HRQoL of patients with PBC was impaired in terms of nonfavorable disease status according to the expectations of patients, but not according to objective disease parameters. Substantial discrepancies between patients’ perspectives and objective parameters were observed, which highlights the need for better patient guidance among patient with PBC.