Online hemodiafiltration (online HDF) is a new hemodialysis technique combining convection and diffusion and thus also enabling the purification of large molecules. As yet, only a small number of clinical experiences have been published about the effectiveness and safety of online HDF. We present a prospective and observational study conducted on 31 patients treated with online HDF in our center in the last 4 years. The purpose of the study is to compare the evolution of the following aspects before and after starting online HDF: dose of dialysis, purification of medium-sized/large molecules, inflammation, nutrition, Ca-P metabolism, anemia, and intradialytic complications. Online HDF increased Kt/V to 31.0% (p > 0.001) and reduced postdialysis beta(2)-M to 66.4% (p > 0.001). The rest of the parameters analyzed did not vary significantly. During online HDF, episodes of symptomatic hypotension fell by 45% in relation to conventional hemodialysis, and no relevant complication occurred. Online HDF is very useful in patients in whom we need to increase replacement therapy, such as patients with a large body surface, those in whom we suspect a residual syndrome or those who have been receiving dialysis for a long time and for whom we wish to prevent amyloidosis. Online HDF is safe and better tolerated than conventional hemodialysis.