Systemic candidiasis is a significant cause of late-onset infection in VLBW neonates, affecting 2-5% of these infants. Reports in the literature describing the demographics of affected infants and analyzing risk factors are predominantly from the 1980's. As neonatal care has changed significantly since then, and smaller babies are surviving more often, we sought to review our experience with neonatal candidiasis in the 1990's. A retrospective, case control study design was used. Hospital and nursery databases were searched to find cases; each case was matched with two controls by birth weight (250g strata: ≤750, 751-1000, 1001-1250, 1251-1500) and birth date. Charts were reviewed for risk factors through the age at which the corresponding case had the first positive systemic culture. 15 VLBW neonates with systemic candidiasis were studied. The mean birth weight was 826±202g (range, 555-1120) and mean gestational age 27.7±2.3 weeks. These infants represent 2.7% of <1250g babies admitted June, 1993-June 1997, with the incidence highest (3.1%) in the smallest birth weight stratum. The mean age at first positive systemic culture was 24 days (range 8-54). Candida albicans was most common (67%), followed by C. parapsilosis. Two dual infections occurred; one with C. albicans and C. parapsilosis, the other with C. albicans and C. glabrata. 14 had fungemia; 7 (50%) of these had concomitant funguria. One infant had funguria without fungemia. No positive CSF cultures were found. 73% of cases were male vs. 53% of controls (p=.33). Vaginal delivery was more frequent in cases (73 vs. 53%). There was a trend toward more antibiotic use in cases (15 days vs. 12 days, p=.08). There was no detectable difference in steroid use, central venous catheters, intubation, hyperglycemia, or use of total parenteral nutrition and lipids. The cases had more complications of prematurity, specifically necrotizing enterocolitis and intraventricular hemorrhage (p<.04). Mortality was significantly more common in cases (33% vs. 0, p=.002). The average length of stay for survivors was 20 days longer than for controls (p=.075). The cost for all cases was significantly higher than for controls (p=.041), with a difference of $89000. In summary, neonatal candidiasis affects the smallest, sickest babies. These infants suffer disproportionate mortality and incur significantly greater costs. A large, multicenter study should be undertaken to better define risk factors contributing to the incidence of systemic candidiasis in VLBW neonates.