OBJECTIVES: To compare attitudes of mental health (MH) professionals towards trials of methylenedioxymethamphetamine-assisted psychotherapy (MDMA-AP), with a neutrally labelled pharmacotherapy trial. DESIGN: A randomised controlled vignette study design, with experimenters blinded to group condition. SETTING: Participants were recruited online via professional societies. PARTICIPANTS: Psychiatrists, psychologists and MH researchers from across Australia. INTERVENTIONS: Participants were randomly allocated to read a vignette about a trial of either MDMA-AP or a neutrally labelled pharmacotherapy. OUTCOMES: Comparison of the difference in four attitudes towards MDMA-AP and control: How likely they were to (1) recommend participating, or (2) object to participating in the trial; (3) their predicted efficacy; and (4) concerns about the safety of the trial. RESULTS: There were no overall differences between professional's attitudes towards MDMA-AP (n=51) and the control pharmacotherapy (n=43) trial vignettes. Psychiatrists were less likely to recommend participation in the MDMA-AP than the control trial ( CONCLUSIONS: Psychiatrists, but not psychologists or researchers showed more hesitancy in recommending trials of MDMA-AP versus an unknown pharmacotherapy. Experienced MH professionals were more likely to have negative views about MDMA-AP trials than less experienced MH professionals. This may reflect the experience of prior unfulfilled pharmacotherapy innovation or exuberance associated with fewer years of practice. Research into, and implementation of, MDMA-AP may face barriers with certain MH professionals, which will need be addressed if MDMA-AP continues to show promise as an efficacious treatment. TRIAL REGISTRATION NUMBER: The study design was registered with the ANZCTR (ACTRN12620001068954).