Abstract. Background: Invasive candidiasis is a late-onset sepsis that occurs in infants in the neonatal intensive care units (NICU). Our study aimed to evaluate the risk factors and outcomes associated with neonatal candidiasis. Methods: A case-control retrospective study was conducted at Miller Children's Hospital from January 1990 to December 2008. Cases were matched to controls by birth weight category, birth date and gestational age. Results: A total of 161 neonates, 103 cases and 58 controls, were included. Demographics such as age, sex, weight and underlying disease were similar between groups. Mean time to infection was 38 days from NICU admission. Multivariable logistic regression revealed that congenital heart disease (odds ratio [OR], 6.35; 95% CI 1.75–23.03, p = 0.005), total parenteral nutrition (OR, 42.97; 95% CI 3.35–550.55, p = 0.004) and abdominal surgery (OR, 6.35; 95% CI 1.75–23.03, p = 0.005) were independently associated with neonatal candidiasis. Mean NICU stay was longer and more patients died in the case group vs. control groups (103 ± 63 vs. 66 ± 27 days, p < 0.001; 13 vs. 2, p = 0.082). Conclusion: The index of suspicion for neonatal candidiasis should be high in those with risk factors, especially if NICU stay exceeds >38 days. Presumptive antifungal therapy should be initiated promptly and antifungal prophylaxis should be considered in these infants.