Beneficial effects of pyloric botulinum toxin injection have been described in a subgroup of gastroparesis patients. Our aim is to evaluate whether clinical, manometric and/or scintigraphic parameters are able to predict treatment outcome. Forty patients (67% female, age 49 (36–56) years) with decompensated gastroparesis treated with botulinum toxin were included in this retrospective analysis. Objective parameters were high-resolution antroduodenal manometry, gastric emptying rate (scintigraphy), and weight change. Subjective treatment outcome was assessed with a Global Physician Assessment Scale. Binary logistic regression analysis was performed to identify predictors for treatment outcome. Fourteen patients (35%) were symptom-responders, and 65% of patients were short-term weight-responders. For both subjective and objective treatment outcome, no differences were found in manometric and scintigraphic variables between responders and non-responders. Neither clinical nor manometric or scintigraphic variables could predict subjective and objective treatment outcome. In conclusion, symptom improvement is achieved in a subgroup of gastroparesis patients treated with endoscopic pyloric botulinum toxin. Although the majority of patients were able to maintain their baseline weight at short-term follow-up, a substantial group of patients needed nutritional interventions on long-term follow-up. However, none of the demographic, clinical, scintigraphic, or antroduodenal manometry variables were able to predict either subjective or objective treatment outcome.