Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain. We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan-Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25-0.5 microg/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox's proportional hazards analysis. The mean follow-up period was 55.1 +/- 38.9 months in the alfacalcidol treatment group and 41.9 +/- 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin-angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone. These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.