We performed a controlled parallel study comparing the effects of heparin sodium to epoprostenol sodium (prostacyclin sodium, Flolan®) during hemodialysis in 30 dialysis patients. Mean fiber bundle volume loss and dialyzer function were similar with both anticoagulation methods. Intradialytic symptoms occurred in 100% of the epoprostenol dialyses and 88% of the heparin dialyses, but only 10/325 epoprostenol and 3/374 heparin dialysis were discontinued prematurely because of symptoms. Long-term hemodialysis with epoprostenol is safe and effective. Epoprostenol may be a suitable alternative to heparin in some dialysis settings.