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Background. Fast reduction of serum free light chain (FLC) levels correlate with renal recovery in cast nephropathy. Because convection has the capacity to remove proteins of higher molecular weights, we hypothesized that haemodiafiltration (HDF) would be superior to haemodialysis (HD) for FLC clearance. Methods. We retrospectively identified all renal replacement therapy (RRT) sessions performed in multiple myeloma patients with pre- and post-treatment FLC measurements during a 2-year period. Using kinetic modelling, we calculated reduction percentages corrected for net ultrafiltration, effective clearances, net mass removal and Kt/V for both kappa (j) and lambda (k) serum FLC. Results. We analysed 27 (10 HD and 17 HDF) RRT sessions realized in a total of six subjects. HDF resulted in higher FLC removal rates when compared to HD. Moreover, high-efficiency (i.e. substitution volume > 15 L/session) HDF demonstrated median efficient FLC clearances roughly twice superior to high-flux HD for both j (59.0 versus 33.8 mL/min, respectively; P < 0.01) and k (40.5 versus 19.7 mL/min, respectively; P ¼ 0.02) FLC. In postdilution HDF treatments, corrected FLC reduction percentages positively correlated with substitution volumes. Total plasma proteins increased during RRT in the HDF group. Conclusions. This preliminary quantitative study demonstrates the superiority of high-efficiency HDF over highflux HD for serum FLC removal in multiple myeloma patients on RRT. No negative impact on total plasma proteins was noted.