Background and Aim Children with intestinal failure (IF) have abnormal intestinal anatomy, secretion, or motility, which impairs homeostatic mechanisms and can lead to small intestinal bacterial overgrowth (SIBO). We sought to describe clinical features at the time of clinically suspected SIBO by experienced clinicians in children with IF on home parenteral nutrition (PN), review specific challenges of diagnostic testing in this population, and describe potential new diagnostic surrogate markers. Methods A descriptive single‐center retrospective chart review was performed during all episodes of clinically suspected SIBO over 33 months. Information was recorded on clinical symptoms, and diagnostic tests performed. Results Of all patients on home PN, 71% (12/17) had at least one episode of clinically suspected SIBO (mean 1 episode/year, range 1–7); 50% of patients had short bowel syndrome (SBS), and 50% had non‐SBS IF. The average reported symptoms per episode were 1.9 (range 1–5). Children with SBS reported fewer symptoms per episode (1.5) than children with non‐SBS IF (2.3). Diarrhea was the most commonly reported symptom, particularly in children with SBS. Conclusions Children with IF on home PN are a high‐risk group for SIBO. Clinical features of SIBO vary depending on the cause of IF and may mimic symptoms of the underlying condition. Diagnostic tests have innate challenges in this group, and a strong index of clinical suspicion is paramount. Further research is recommended into potential new surrogate markers (urinary metabolite screen, gastric aspirate) for this diagnostically challenging population. Children with intestinal failure (IF) on home parenteral nutrition are a high‐risk group for small intestinal bacterial overgrowth. We identified clinical features during episodes of clinically suspected small intestinal bacterial overgrowth and found variation depending on the underlying cause of IF. Diagnostic tests have innate challenges in children with IF on home parenteral nutrition, and we discuss potential new surrogate markers for this diagnostically challenging population.