The benefits and disadvantages of hemodialyzer reuse is controversial. While biochemical data have suggested potential benefits from reuse, there is dispute over the clinical impact on the patient. Limited data show that reuse is associated with less intradialytic symptoms compared to first use. We conducted a prospective study of acute symptoms during clinical dialysis using new and reused cellulose acetate membrane hollow-fiber dialyzers. A total of 106 sessions using new dialyzers and 871 sessions employing reused dialyzers were monitored. Dialyzers were processed with an automated machine using hydrogen peroxide and peroxyacetic acid as sterilants. We found that, compared to new ones, reused dialyzers were associated with a similar frequency of overall and specific symptoms. In addition, there was no difference in the magnitude of changes in blood pressure during and after the treatments between the two groups. We conclude that maintenance hemodialysis with reused cellulose acetate membrane dialyzers processed with hydrogen peroxide and peroxyacetic acid was not associated with more or fewer subjective symptoms than dialysis with new dialyzers.