Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10 g/dL, and a serum creatinine of 2.0 to 6.0 mg/dL. They were randomized into two target Hb groups: 161 to high Hb (11.0–13.0 g/dL) to receive darbepoetin alfa and low Hb to 160 (9.0–11.0 g/dL) to receive recombinant erythropoietin. The study lasted 48 weeks. Of 154 and 153 patients with adverse events, cardiovascular adverse events developed in 42 and 51 patients in the high and low Hb groups, respectively, with no significant difference in the incidence. All quality of life scores improved in the high Hb group and vitality improved significantly more with high Hb (P = 0.025). The left ventricular mass index (LVMI) remained stable in the low Hb group, but there was a significant decrease in LVMI in the high group (P < 0.001). There were no safety concerns with targeting a higher Hb level during the 48 weeks of this study. Patients with a higher Hb target had comparatively better outcomes with respect to quality of life and LVMI.