Accumulating data from observational studies showed that online hemodiafiltration (OLHDF) might improve survival in chronic hemodialysis (HD) patients. According to this data, the aim of our study was to investigate whether there was a difference in survival of patients treated with OLHDF compared to standard, conventional HD. We included 85 prevalent patients with end-stage renal disease (ESRD) treated with HD as a method of renal replacement therapy (RRT) for more than three months. Patients were previously treated with HD and divided into two groups: in 42 patients new treatment with OLHDF was introduced, and 43 patients were treated with HD. Both groups were followed over a period of 36 months. The study showed significantly better survival of patients treated with OLHDF, compared to the survival of patients treated with HD in the whole study population, as well as in the subgroups of diabetics, of patients who were on RRT with HD for more than five years and of the patients who were older than 65 years. In the nondiabetics, patients who were on RRT for less than five years and in the patients who were younger than 65 years, survival results in the OLHDF group were not significantly better compared to those in the HD group. As in our study, there are accumulating data from observational studies that HDF may improve survival in chronic HD patients, but new, prospective randomized trials are needed to support evidence about this hypothesis.