When treating patients with methotrexate (MTX) the most frequently reported adverse effects (AE) are gastrointestinal (GI) with nausea being reported by 10-20%. If intolerable AE of oral MTX persist, switching from oral to subcutaneous (SC) or intramuscular (IM) administration is common. However, this approach is largely empirical and the evidence is inconsistent. To our knowledge, this will be the first study to estimate the change in GI AE of switching from oral to SC MTX. Methods: A retrospective postal survey was sent to patients who had changed from oral MTX to SC MTX. GI AE was rated by visual analogue scale (VAS) regarding frequency and intensity of nausea, frequency of vomiting and frequency of discomfort. All participants gave informed consent. No further ethical clearance was necessary according to national law. Results: Of the sample 39/57 (68.4%) responded. Significant reductions in VAS were found in three of four primary outcome measures for GI AE. Only frequency of vomiting was not significantly reduced. Conclusion: Our findings support the common practice of switching from oral to SC MTX to alleviate GI AE, however, additional research is needed in order to clarify this rarely studied subject.