Introduction: Cystoisospora belli infection is one of the most important causes of watery diarrhea in patients with HIV and causes high rates of morbidity and mortality. Methods: A retrospective study was conducted in patients with HIV and diarrhea by C. belli. Clinical and laboratory characteristics were collected by analyzing clinical records. Results: Four had recurrent diarrhea despite receiving secondary prophylaxis with cotrimoxazole and specific treatment, two of which had a good viral and immunological response to highly active antiretroviral therapy (HAART) at the time of diagnosis and antiparasitic treatment. While the remaining three did not receive prophylaxis, neither did HAART (two of them), but they responded well to treatment. Conclusions: C. belli is an important cause of diarrhea in HIV patients on HAART and prophylaxis, being able to have different clinical evolution. We suggest that persistent infection may be due to drug failure by intrinsic or extrinsic to the parasite causes, or to defects in restoration of the intestinal immune system, or both.