BACKGROUND: Adenovirus disease (ADVd) is a significant burden in pediatric hematopoietic stem cell transplant (HSCT) recipients. However, current knowledge of risk factors associated with poor clinical outcome and the effectiveness of antiviral therapy are not well understood. This study determined the relationship between transplant characteristics and risk of ADVd and also compared time to resolution of disease between pediatric patients who did and did not receive antiviral therapy. METHODS: We conducted a retrospective, single-center cohort study of pediatric patients undergoing HSCT at Duke University (2005-2016). Cases of ADVd were defined a priori using a classification tool. Cox proportional hazards (CPH) regression models were used to compare the hazard of ADVd between HSCT recipients differing by type of transplant and type of conditioning regimen. The hazard of time to resolution of ADVd by antiviral therapy (cidofovir, brincidofovir, both, or neither) was compared. RESULTS: Ninety-three of 830 subjects had ADVd post-HSCT (11.2%). Umbilical cord transplant (UCT) recipients had 2.30 (95% CI 1.57, 6.90, P = .002) higher hazard of developing ADVd compared to non-cord allogeneic transplants, and 6.30 higher (95% CI 2.70, 19.61, P < .001) hazard compared to autologous transplants. Subjects who did not receive antiviral therapy experienced earlier resolution of ADVd compared to subjects who received therapy, even after adjusting for subjects with disseminated disease (HR [95% CI]: 3.75 [1.57, 8.93], P = .003). CONCLUSIONS: Pediatric UCT recipients are at a higher risk for ADVd. Antiviral therapy was not associated with an earlier resolution of ADVd, even in patients with higher disease burden.