Background: The therapeutic role of <smlcap>L</smlcap>-carnitine (LC) on the anemia of chronic hemodialized patients is still controversial. In order to clarify the long-term effects of LC administration on renal anemia, an open, observational 12-month study was performed. Methods: Twenty stable outpatients undergoing hemodialysis were administered LC 900 mg p.o. daily for 12 months. The recombinant human erythropoietin (rHuEPO) dose was adjusted monthly when necessary to maintain the target hemoglobin (Hb) levels. Results: The free LC level increased, while the acyl/free LC ratio decreased significantly 3 months after administration and was then maintained until the end of the study. There was no difference in Hb levels and the erythropoietin resistance index (ERI) during the study period. However, it was observed that ERI decreased significantly in 7 out of 18 patients (responders) 5 months after LC administration and was maintained thereafter (almost 40% reduction of the rHuEPO dose). The acyl/free carnitine ratio at baseline was the most contributing factor distinguishing responders from nonresponders. Conclusion: Although the beneficial effect of LC supplementation on renal anemia was not observed in all patients, at least 40% of the patients (responders) showed a significant improvement in ERI after long-term LC administration.