Objectives <p>Primary objective was to compare the performance of proadrenomedullin (ProADM) and procalcitonin (PCT) for diagnosing clinically documented infections (CDI)/microbiologically documented infections (MDI)/fever without focus (NF) in children with cancer having febrile neutropenia (FN). The secondary objective was&#xa0;to compare the prognostic utility of PCT and ProADM for identifying adverse clinical outcome.</p> Methods <p>Cancer patients (aged ≤ 18&#xa0;years) presenting with FN were included; those who had received antibiotics within the last 14&#xa0;days were excluded. Serum PCT and ProADM were estimated on days 1, 3 and 7 of enrolment. Adverse outcome was defined in terms of clinical non-response and day 30 mortality.</p> Results <p>We recruited 345 children. PCT in children with MDI were significantly higher than those with CDI on day 1 (<i>P</i> = 0.031) and day 7 (<i>P</i> &lt; 0.001); PCT ≥ 0.21&#xa0;ng/mL on day 1 had a 77% sensitivity and 44% specificity for diagnosis of MDI; the area under receiver operating characteristic curve (95 CI%) 0.601 (0.49, 0.71). ProADM did not differentiate between MDI and CDI. PCT and ProADM on day 1 did not predict the need for second line antibiotics. PCT ≥ 0.21&#xa0;ng/mL on day 1 was predictive of MDI (<i>P</i> = 0.041) and PCT ≥ 1.77&#xa0;ng/mL on day 7 was an independent predictor of day-30 mortality.</p> Conclusions <p>PCT is effective in differentiating between MDI, CDI, and NF in children with FN, and also predicts the day 30 mortality.</p>