There are no consensus guidelines for management of pediatric oncology patients presenting with fever and nonneutropenia, with limited research into the outcomes of withholding empiric i.v. antibiotics. We conducted a prospective cohort study assessing the safety and efficacy of observing well-appearing patients presenting with fever and nonneutropenia (absolute neutrophil count >/= 500 cells/mm(3) ). Of 238 episodes, 82.7% patients were observed with no infectious complications and low overall incidence of bacteremia (3.4%). There were no significant differences in individual clinical variables. We propose that observation alone in some well-appearing febrile pediatric oncology patients is safe and limits the use of unnecessary empiric antibiotics.