Purpose: Treatment adherence is crucial in patients with rheumatoid arthritis (RA). The device used by the patients for self-injections may influence adherence to methotrexate (MTX) treatment. A MTX-autoinjector has been recently marketed in Europe. This crossover survey compared this MTX-autoinjector (MTX-autoinjector A) and an already existing MTX-autoinjector (MTX-autoinjector B) from the patients' perspective. Patients and methods: A total of 100 patients with moderate to severe RA using MTX-autoinjector A (N=35) or MTX-autoinjector B (N=65) were interviewed by an independent Global Market Research Company. Face-to-face interviews were performed using a computer-assisted personal interview system. Evaluation of the unfamiliar MTX-autoinjector was performed once the patients had received information, seen a demonstration, and performed a virtual testing. Results: A substantial advantage in favor of the MTX-autoinjector A was found with respect to all surveyed indicators. Respectively, 95% and 55% of the users of MTX-autoinjectors A and B claimed to be very or totally satisfied with their familiar MTX-autoinjector. With respect to several specific characteristics, 91% and 60% of the users of MTX-autoinjectors A and B were very or totally satisfied with their familiar MTX-autoinjector, 29% and 77% found the unfamiliar MTX-autoinjector better, and 26% and 73% were interested in trying the unfamiliar MTX-autoinjector. Injection mode (with no push button) and end-of-injection recognition system (with audible signal) were identified as key features explaining a stronger preference for MTX-autoinjector A. Conclusion: Even though deserving further studying, these findings are expected to guide clinicians when prescribing or renewing prescription of MTX-autoinjector, in particular in poor or non-compliant patients. In a context of growing interest in shared decision-making, the objective would be to choose with each patient the best suited MTX-autoinjector, and ultimately, to obtain a better treatment adherence.