We report a case of acute hemolytic anemia in a 21-year-old Nigerian woman after high-dose misoprostol (4 mg), used for medical abortion. The major causes of inherited or immune hemolytic anemia were excluded. The patient's peripheral blood smear showed acanthocytes and anisopoikilocytosis, which progressively disappeared in the days postingestion. We evaluated RBC features, and we observed reduced RBC Na+ and K+ content and abnormalities in membrane cation transport pathways and in Ca2+ activated K+ channel (Gardos channel), suggesting possible direct effects of misoprostol on RBCs. Although further studies need to be carried out, the present case suggests that high-dose misoprostol, a prostaglandin E1 analogue, severely affects RBC features and causes an acquired acute hemolytic anemia, which is self-limited when misoprostol is withdrawn.