OBJECTIVE Burn patients are particularly vulnerable to infection, and an estimated half of all burn deaths are due to infections. This study explored risk factors for healthcare-associated infections (HAIs) in adult burn patients. DESIGN Retrospective cohort study. SETTING Tertiary-care burn center. PATIENTS Adults (≥18 years old) admitted with burn injury for at least 2 days between 2004 and 2013. METHODS HAIs were determined in real-time by infection preventionists using Centers for Disease Control and Prevention criteria. Multivariable Cox proportional hazards regression was used to estimate the direct effect of each risk factor on time to HAI, with inverse probability of censor weights to address potentially informative censoring. Effect measure modification by burn size was also assessed. RESULTS Overall, 4,426 patients met inclusion criteria, and 349 (7.9%) patients had at least 1 HAI within 60 days of admission. Compared to 6 times as likely to acquire an HAI (HR, 6.38; 95% CI, 3.64-11.17); and patients with >20% TBSA were >10 times as likely to acquire an HAI (HR, 10.33; 95% CI, 5.74-18.60). Patients with inhalational injury were 1.5 times as likely to acquire an HAI (HR, 1.61; 95% CI, 1.17-2.22). The effect of inhalational injury (P=.09) appeared to be larger among patients with ≤20% TBSA. CONCLUSIONS Larger burns and inhalational injury were associated with increased incidence of HAIs. Future research should use these risk factors to identify potential interventions. Infect Control Hosp Epidemiol 2017;38:1441-1448.