Vitamin D deficiency has been linked to cardiovascular disease and early mortality in patients on hemodialysis; however, it is not known if the same association exists at earlier stages of chronic kidney disease. To determine this we enrolled 168 consecutive new referrals to a chronic kidney disease clinic over a 2 year period and followed them for up to 6 years. All patients were clinically stable and had an estimated glomerular filtration rate (eGFR) at stage 2 or less and were without an imminent need for dialysis. Baseline 25-hydroxyvitamin D levels directly and significantly correlated with eGFR. After an average follow-up of 48 months, 48 patients started dialysis and 78 had died. In crude analyses, 25-hydroxyvitamin D predicted both time to death and end-stage renal disease. A dual-event Cox's model confirmed 25-hydroxyvitamin D as an independent predictor of study outcomes when adjusted for age, heart failure, smoking, C-reactive protein, albumin, phosphate, use of converting enzyme inhibitors or angiotensin receptor blockers, and eGFR. Our study shows that plasma 25-hydroxyvitamin D is an independent inverse predictor of disease progression and death in patients with stage 2-5 chronic kidney disease.