Background & aims: Sufficient protein intake is of great importance in hemodialysis (HD) patients, especially for maintaining muscle mass. Daily protein needs are generally estimated using bodyweight (BW), in which individual differences in body composition are not accounted for. As body protein mass is best represented by fat free mass (FFM), there is a rationale to apply FFM instead of BW. The agreement between both estimations is unclear. Therefore, the aim of this study is to compare protein needs based on either FFM or BW in HD patients. Methods: Protein needs were estimated in 115 HD patients by three different equations; FFM, BW and BW adjusted for low or high BMI. FFM was measured by multi-frequency bioelectrical impedance spectroscopy and considered the reference method. Estimations of FFM x 1.5 g/kg and FFM x 1.9 g/kg were compared with (adjusted)BW x 1.2 and x 1.5, respectively. Differences were assessed with repeated measures ANOVA and Bland–Altman plots. Results: Mean protein needs estimated by (adjusted)BW were higher compared to those based on FFM, across all BMI categories (P < 0.01) and most explicitly in obese patients. In females with BMI >30, protein needs were 69 ± 17.4 g/day higher based on BW and 45 ± 9.3 g/day higher based on BMI adjusted BW, compared to FFM. In males with BMI >30, protein needs were 51 ± 20.4 g/day and 23 ± 20.9 g/day higher compared to FFM, respectively. Conclusions: Our data show large differences and possible overestimations of protein needs when comparing BW to FFM. We emphasize the importance of more research and discussion on this topic.