Abstract Background and Aims Chronic volume overload is a major contributor to cardiovascular mortality in patients receiving maintenance hemodialysis (HD). Hence, accurately assessing volume status in this population is crucial. Bioelectrical impedance analysis (BIA) is a validated, non-invasive, and straightforward bedside technique that estimates total body water (TBW), extracellular water (ECW), intracellular water (ICW), and over hydration (OH). However, it is not suitable for use in patients with limb amputation or metallic medical devices. On the other hand, lung ultrasound (LUS) is used to evaluate extravascular lung water (EVLW) and has been shown to predict all-cause mortality and cardiac events in HD patients. Although a 28-zone LUS is the reference standard for LUS studies, recent studies have shown that an 8-zone LUS protocol can be as accurate. The aim of this study was to compare the performance of an 8-zone LUS protocol with bioelectrical impedance analysis to evaluate hydration status in an outpatient haemodialysis unit. Method Adult patients under thrice-weekly 4h HD sessions using high-flux membrane dialyzers for at least 1 month were prospectively enrolled between June and August 2022. We excluded patients with systemic infections, advanced neoplasia, metallic medical devices, decompensated cirrhosis, and limb amputations. The dry weight (DW) was established by the attending nephrologist, blind to the results. All measurements were performed in the first session of the week. BIA was assessed before HD using a portable whole body BIA device (BCM—Fresenius Medical Care D GmbH) and the OH was normalized to ECW. LUS using 8-zone protocol was performed before and after HD, with patients in the near-to-supine or supine position using a 2–5 MHz convex probe (Acuson X150®, Siemens, Germany), and the total number of B lines was recorded. Results A total of 37 patients with median age of 60 (IQR 15) years, 75% males, 65% with residual diuresis >300 mL/24 h were included. The median HD vintage was 9 (IQR 10) months, and median body mass index (BMI) of 22.7 (IQR 9) Kg/m2. At the beginning of HD, the median systolic blood pressure (BP) was 140 (IQR 24) mmHg and the median diastolic BP was 79 (IQR 16) mmHg. The median interdialytic weight gain was 4.2% (IQR 2.8) and median ultrafiltration (UF) was 2600 (IQR 1300) mL. The BIA showed median TBW of 38.2 (IQR 11) L, ECW 18.2 (IQR 7.73) L, ICW 20.8 (IQR 6.55) L, and normalized OH 0.138 (IQR 0.147). There was a positive correlation between BMI, TBW (r = 0.375, p = 0.045), and ECW (r = 0.486, p = 0.006), but not with ICW (r = 0.061, p = 0.755), nor normalized OH (r = 0.14, p = 0.468). Systolic BP, but not diastolic, was correlated with the water volume measured in both compartments (ECW: r = 0.498, p = 0.005; ICW: r = 0.421, p = 0.023, TBW: r = 0.423, p = 0.022). The 8-zone LUS showed a statistically significative (p<0.001) reduction in the number of B lines between pre and post HD evaluation (16.5 (IQR 17.25) lines to 8.5 (IQR 10.25) lines). Total evaluation time was under 8 minutes. When comparing LUS before HD with BIA assessment we found that the number of B lines correlated with the normalized OH (r = 0.454, p = 0.018), ECW (r = 0.501, p = 0.007), TBW (r = 0.418, p = 0.030), but not ICW (r = 0.239, p = 0.23). The total number of B lines post HD was also correlated with the ECW (r = 0.568, p = 0.002), TBW (r = 0.465, p = 0.017), and normalized OH (r = 0.408, p = 0.039). Conclusion The 8-zone LUS protocol provides a quick and efficient way to evaluate patients prior to HD sessions. Our study reveals a strong correlation between the total number of B lines determined by the 8-zone protocol and BIA parameters such as TBW, ECW, and normalized OH. This demonstrates that the 8-zone protocol can effectively be used in routine evaluations of HD patients. Although these techniques reflect different over-fluid compartments, they have a complementary role for fluid overload determination and dry weight guidance.