Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH) D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Methods. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH) D levels and immunological/inflammatory markers. Results. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range IQR: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval CI, 2.0-70.0, P= .04) for a 2-fold increase in latest 25(OH) D level. There was no association between 25(OH) D and the occurrence of AIDS or non-AIDS-defining events (P >.05). In patients with current 25(OH) D < 10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P =.04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P =.76). Conclusions. Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.