Introduction: Iron deficiency (ID) is common in patients with chronic kidney disease (CKD) but remains under-diagnosed and its prognosis poorly documented in the absence of anemia. The aim of the study was to assess the relationship between ID and the risk of major adverse outcomes in patients with CKD. Methods: Using data from the French Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) cohort which included and followed over five years, 3,033 patients with CKD stages 2 to 5 CKD, we estimated the prevalence of ID, defined by a ferritin level < 100 mg/L and/or a transferrin saturation < 20%, and associated hazard ratios (HR) of kidney failure with replacement therapy, kidney failure defined by an eGFR < 15 mL/min per 1.73 m2 or initiation of kidney replacement therapy, all-cause mortality, and death or hospitalization for heart failure. Results: Baseline prevalence of ID in the cohort (66% men; mean age 67 ± 13 years) was 50% (48-52). Mean hemoglobin was 13 ± 1.7 g/dL, and only 31% of patients with ID also had a hemoglobin < 12 g/dL. In 2,803 patients with CKD stages 2-4 at baseline, ID was associated with significant increased risk of kidney failure, and of kidney failure with replacement therapy, with HRs adjusted for confounders and hemoglobin level of 1.22 (1.03-1.45) and 1.57 (1.27-1.94), respectively. Adjusted HRs for all-cause mortality and hospitalization or death for heart failure, were 1.31 (1.04-1.66) and 1.38 (1.07-1.80), respectively. Conclusion: This study shows that ID is significantly associated with the risk for kidney failure, all-cause mortality, and heart failure, independent of the presence of anemia.