Abstract Background [¹¹C]Metoclopramide is a new radiotracer for investigating the activity of P-glycoprotein at the blood-brain barrier. A highly stable and reproducible radiosynthesis is a prerequisite for clinical studies applying [¹¹C]metoclopramide or other ¹¹C-labelled radiotracers, therefore all potential pitfalls must be identified and monitored to allow a stable process. Results Long-term production (n = 94 in a time range of approximately 2 years) of [¹¹C]metoclopramide synthesized on two commercially available synthesizers yielded 3.9 ± 2.0 GBq of product with a molar activity of 132 ± 164 GBq/μmol and an overall success rate of 93%. During all successful productions, the product quality was in accordance with the recommendations of the European Pharmacopoeia. The most common pitfalls that were identified for the radiosynthesis included poor turnover into [¹¹C]CH₃OTf, decomposition of the solvent or insufficient semi-preparative HPLC performance. Conclusion The study provides long-term insight in the improved, robust and stable preparation of [¹¹C]metoclopramide for human use.