Background: Patients with cirrhosis often develop hyperdynamic circulation with increased cardiac output, heart rate, and redistribution of the circulating volume with expanded plasma volume (PV). PV determination is part of the evaluation of patients with cirrhosis, but gold-standard methods are invasive, expensive, and time-consuming. Therefore, other estimations of PV would be preferable, and the aim of this study was therefore to study if PV, as assessed by a simplified algorithm based on hematocrit and weight, can replace the gold-standard method. Methods: We included 328 patients with cirrhosis who had their PV assessed by the indicator dilution technique as the gold-standard method (PV_I-125). Actual PV was estimated as PV_a = (1 − hematocrit)·(a + (b·body weight)). Ideal PV was estimated as PV_i = c · body weight, where a, b, and c are constants. Results: PV_I-125, PV_a, and PV_i were 3.99 ± 1.01, 3.09 ± 0.54, and 3.01 ± 0.65 (Mean ± SD), respectively. Although PV_I-125 correlated significantly with PV_a (r = 0.72, p < 0.001), a Bland–Altman plot revealed wide limits of confidence. Conclusions: The use of simplified algorithms does not sufficiently estimate PV and cannot replace the indicator dilution technique.