Encapsulating peritoneal sclerosis (EPS) represents a critical complication of peritoneal dialysis (PD). EPS is characterized by abdominal discomfort, often leading to fatal outcomes with limited pharmaceutical and surgical options. Herein is described a case of EPS with a favorable outcome in an African male treated with PD for 15 years. Repeated courses of prednisone and tamoxifen significantly attenuated the abdominal symptoms and the peritoneal membrane thickening. This case suggests a time dependent effect of medical treatment encouraging clinical efforts to maintain a mild immunosuppressant regimen and tamoxifen in the presence of EPS also on the long run. Future and ad hoc studies should test this hypothesis.