Background. Although haemodialysis (HD) leads to alterations of systemic haemodynamics that can be monitored using dilution methods, there is a lack of data on the diagnostic and prognostic significance of haemodynamic monitoring during routine HD. Methods. In this multicentre study, we measured cardiac index (CI), access flow (AF) and central blood volume index (CBVI) during a single HD session in stable HD patients (n ¼ 215) using the Transonic HD03 monitor (Transonic, Ithaca, NY, USA). Systemic CI (SCI) was defined as CI corrected for AF. In a subset of patients (n ¼ 82), total end-diastolic volume index (TEDVI) and total ejection fraction (TEF) were derived from dilution curves. Data were correlated with clinical parameters, cardiac biomarkers and bioimpedance measurements (body composition monitor; Fresenius Medical Care, Homburg, Germany). Mortality was assessed prospectively after a median follow-up of 2.6 years. Results. Median CI, CBVI and AF were 2.8 L/min/m2 (interquartile range 2.4–3.4), 15 mL/kg (14.5–15.7) and 980 mL/min (740–1415), respectively, at the beginning of HD. At the end of HD, CI, CBVI and AF significantly fell by 10% (22 to 3, P < 0.0001), 9% (23 to 3, P < 0.0001) and 4% (13 to 5, P ¼ 0.0004), respectively. Peripheral resistance (PR) increased slightly (P ¼ 0.01) and blood pressure fell by 6/3 mmHg to 128/63 mmHg (P < 0.0001). Independent predictors of DCI were age and ultrafiltration rate, whereas AF, overhydration and PR were protective. TEF was strongly associated with mortality [area under the dilution curve 0.77, P < 0.0001], followed by TEDVI (0.72, P ¼ 0.0002) and SCI (0.60, P ¼ 0.02). Conclusions. HD leads to a reduction of CI due to ultrafiltration. Haemodynamic monitoring identifies a significant number of HD patients with cardiac impairment that are at risk for increased mortality.