We evaluated whether the likelihood of developing invasive candidiasis (IC) differed depending upon the anatomic site of Candida colonization in 182 surgical intensive care unit (SICU) patients who participated in a randomized trial of fluconazole to prevent candidiasis. We also determined the impact of Candida colonization of different anatomic sites on all-cause SICU and hospital mortality. A total of 2851 surveillance fungal cultures collected from 5 anatomic sites were analyzed. There was a statistically significant difference in the frequency of IC comparing patients with and without urinary (13.2% versus 2.8%, P = .02), respiratory (8.0% versus 1.2%, P = .04), and rectum/ostomy (8.4% versus 0%, P = .01) colonization. Patients with negative rectum/ostomy cultures and patients with both negative urine and respiratory tract cultures did not develop IC. Candiduria detected at any time in the SICU was independently associated with SICU mortality (odds ratio, 2.86; 95% confidence interval, 1.05-7.74). Surveillance fungal cultures of particular anatomic sites may help differentiate patients at higher risk of developing IC from those at low risk.