Blenderised tube feeds (BTF) have become a popular alternative to commercial formula (CF) for enterally fed children. This study sought to compare gastrointestinal (GI) symptoms, GI inflammation, and stool microbiome composition between children receiving BTF or CF. This prospective cohort study involved 41 gastrostomy-fed children, aged 2–18 years, receiving either BTF (n = 21) or CF (n = 20). The Paediatric Quality of Life Inventory Gastrointestinal Symptoms Scale (GI-PedsQL) was used to compare GI symptoms between the groups. Anthropometric data, nutritional intake, nutritional blood markers, faecal calprotectin levels, stool microbiota, and parental satisfaction with feeding regimen were also assessed. Caregivers of children on BTF reported greater GI-PedsQL scores indicating significantly fewer GI symptoms (74.7 vs. 50.125, p = 0.004). Faecal calprotectin levels were significantly lower for children receiving BTF compared to children on CF (33.3 mg/kg vs. 72.3 mg/kg, p = 0.043) and the BTF group had healthier, more diverse gut microbiota. Subgroup analysis found that 25% of caloric intake from BTF was sufficient to improve GI symptoms. The CF group had better body mass index (BMI) z-scores (−0.7 vs. 0.5, p = 0.040). Although growth was poorer in children receiving only BTF in comparison to the CF group, this was not seen in children receiving partial BTF. A combination of BTF and CF use may minimise symptoms of tube feeding whilst supporting growth.