Background. Thrombotic thrombocytopenic purpura (TTP) is a clinically rare thrombotic cardiovascular and microvascular disease. The purpose of this study was to observe the clinical efficacy and safety of plasma exchange in the treatment of TTP. Methods. A total of 16 TTP patients who underwent plasma exchange from January 2015 to December 2020 were selected. The clinical data of all patients were collected for retrospective analysis. The effective rate of treatment, the changes of blood cell count before and after treatment, and adverse reactions during treatment were analyzed. Results. A total of 50 plasma exchanges were performed in 16 TTP patients. After plasma exchange treatment, there were 4 invalid and 12 improved patients. The total effective rate of plasma exchange in patients with TTP was 75.0%. After treatment, platelet count (PLT) and hemoglobin (Hb) levels were significantly increased in TTP patients. Compared with before treatment, lactate dehydrogenase (LDH), indirect bilirubin (IBIL), total bilirubin (TBIL), and broken red blood cells were significantly reduced. In addition, 3 adverse reactions occurred in 50 plasmapheresis procedures, and the incidence of adverse reactions was 6.0%. Conclusion. Plasma exchange therapy has a good therapeutic effect on TTP and can significantly improve abnormal blood cell count in patients with high safety.