Introduction: The incidence of vitamin D deficiency in critically ill patients has been reported to range from as low as 17% to as high as 79%. Data regarding the relationship between 25-hydroxyvitamin D levels and outcomes in the medical intensive care unit are sparse. The goal of the study was to evaluate the prevalence of 25-hydroxyvitamin D deficiency in the medical intensive care unit and its relationship with outcomes.Method: This was a retrospective study in a medical intensive care unit (MICU) at an inner city community hospital. The study period was between October 2009 and February 2010.Results: Of the 932 patients admitted during the study period, 25-hydroxyvitamin D vitamin D (25(OH)D) levels were available in 523 (53%); 86 of them were excluded from the study due to readmission to the intensive care unit. Deficiency was defined as 0 to 19.9 ng/dL 25(OH)D levels, insufficiency as 20 to 29.9 ng/dL, and normal levels as ≥30 ng/dL. Of the 437 patients studied, 25(OH)D deficiency was identified in 340 (77.8%), insufficiency in 74 (16.9%), and normal levels in 23 (5.3%) patients. Patients with 25(OH)D deficiency/insufficiency were younger (P = 0.015), were male (P = 0.001), and had kidney disease (P = 0.017) and lower total serum calcium levels (P = 0.003). Hospital mortality was higher in patients with 25(OH)D deficiency (P = 0.01). No differences in ventilator days or length of stay in the MICU were evident among the three groups. Analysis by multiple logistic regression demonstrated that acute physiology and chronic health evaluation (APACHE) IV score ((odds ratio (OR) 1.036; 95% confidence interval (CI) 1.024-1.048, P < 0.0001), ventilator requirement (OR 7.7; 95% CI 4.3-13.98, P < 0.0001), 25(OH) D levels(OR 0.942; 95% CI 0.942-0.904, P < 0.0005) and 25(OH) D deficiency (OR 8.7; 95% CI 1.03-72.8, P < 0.0469) showed statistical significance. There was no association between 25(OH)]D insufficiency and hospital mortality. The mean 25(OH)D level of survivors (27.9 ± 9.7 ng/dL) was higher than for non-survivors (9.7 ± 4.7 ng/dL; P < 0.0001).Conclusions: The study results demonstrate an association between 25(OH)D deficiency and hospital mortality in MICU patients. A randomized prospective study to evaluate the effect of vitamin D replacement therapy on mortality is warranted.