RATIONALE: Obesity is a global health concern, with intragastric balloon (IGB) placement serving as a nonsurgical intervention for weight management. However, intolerance due to severe gastrointestinal side effects often leads to premature removal, limiting its effectiveness. Botulinum toxin A (BTX-A) injection has been proposed as a potential strategy to improve IGB tolerance by modulating gastric motility. PATIENT CONCERNS: This study reports a case series of patients who developed severe intolerance to IGB placement, including persistent nausea, vomiting, fluid intolerance, dehydration, and reduced urine output, necessitating medical intervention. DIAGNOSES: Patients were diagnosed with IGB intolerance due to obstructive gastric effects, characterized by impaired gastric emptying and intolerance to oral fluids, leading to dehydration and electrolyte imbalances. INTERVENTIONS: A total of 14 patients with IGB intolerance were treated with 500 U of BTX-A injected around the pyloric canal. Prokinetic drugs were also administered to support gastric motility. Patients were monitored for 6 months following the intervention. OUTCOMES: Among the 14 patients, 11 (78.57%) showed a significant improvement in fluid tolerance within 12 hours of BTX-A injection and were able to retain the IGB without additional complications. Three patients (21.43%) did not improve and required early IGB removal. No major adverse effects related to BTX-A injection were observed. LESSONS: BTX-A injection appears to be a promising adjunctive therapy to improve IGB tolerance in patients experiencing severe intolerance. These findings suggest a potential role for BTX-A in reducing the need for premature balloon removal, thereby enhancing weight loss outcomes. However, further randomized controlled trials with larger sample sizes are needed to confirm its efficacy, optimize dosage, and establish standardized treatment protocols.