Abstract Background and Aims Peritoneal dialysis (PD) has the advantages of not causing rapid changes in the body fluid levels or solute contents in the blood due to the continuous treatment on all days of the week, and of not needing the patients to visit the hospital 3 times a week or lie on a bed for 4 hours to receive treatment. PD alone can, however, not adequately remove all the uremic toxins and excess water, and the patients are likely to be resistant to erythropoiesis-stimulating agents (ESA). These drawbacks could be potentially improved if PD and hemodialysis (HD) were used together. The aims of the present study were to clarify the changes in the body weight, serum β2-microglobulin (β2MG) level, and resistance to ESA in PD patients switched from PD alone to PD-HD hybrid therapy (hybrid therapy). Methods The data of seven patients who were switched from PD alone to PD-HD hybrid therapy at our hospital were retrospectively analyzed to determine the changes in the body weight, serum β2MG level, dose of ESA (Darbepoetin Alfa) and the hemoglobin level before and at 3 months after the switch to hybrid therapy; in hybrid therapy, the patient received HD once a week and did not receive PD on that day. We also carried out a questionnaire survey to determine the changes in the feeling of well-being and quality of life of the patients after the switch to hybrid therapy. Results and Discussion The body weight decreased significantly from 67.4 ± 11.8 kg to 63.7 ± 8.7kg (p = 0.0345) after the switch from PD alone to PD-HD hybrid therapy, indicating that the control of the body fluids was much easier with hybrid therapy than with PD alone. The mean serum β2MG level in the patients decreased from 37.3 ± 11.6 μg/mL to 32.6 ± 5.9 μg/mL (p = 0.1607, not significant), ; in particular, in those patients in whom the serum β2MG levels were over 30 μg/mL, the level decreased significantly from 42.5 ± 8.7 μg / mL to 34.4 ± 6.1 μg / mL (p = 0.0337). The dose of ESA decreased significantly in all patients from 193 ± 74 μg/month to 69 ± 38 μg/month (p = 0.006), while the hemoglobin level remained unchanged (from 10.2 ± 1.7 g/dL to 11.2 ± 1.2 g/dL, p = 0.1406). In the questionnaire survey, almost all the patients expressed positive feelings about the switch of the treatment modality, such as “it became easier to go up the stairs,” “improved working efficiency,” and “comfortable feeling.” Since the peritoneum was allowed to rest once in a week, on the day of the HD, it could also preserve peritoneal functions. Therefore, hybrid therapy was also considered to be effective from the viewpoint of performing PD over the long term. Conclusion We can expect easier management of the body fluid, efficient β2MG removal, and improvement of ESA resistance by switching the dialysis treatment modality from PD alone to HD-PD hybrid therapy.