BackgroundMulti-grip myoelectric hand prostheses (MHPs), with five movable and jointed fingers, have been developed to increase functionality. However, literature comparing MHPs with standard myoelectric hand prostheses (SHPs) is limited and inconclusive. To establish whether MHPs increase functionality, we compared MHPs with SHPs on all categories of the International Classification of Functioning, Disability, and Health-model (ICF-model).MethodsMHP users (N = 14, 64.3% male, mean age = 48.6 years) performed physical measurements (i.e., Refined Clothespin Relocation Test (RCRT), Tray-test, Box and Blocks Test, Southampton Hand Assessment Procedure) with their MHP and an SHP to compare the joint angle coordination and functionality related to the ICF-categories ‘Body Function’ and ‘Activities’ (within-group comparisons). SHP users (N = 19, 68.4% male, mean age = 58.1 years) and MHP users completed questionnaires/scales (i.e., Orthotics and Prosthetics Users’ Survey—The Upper Extremity Functional Status Survey /OPUS–UEFS, Trinity Amputation and Prosthesis Experience Scales for upper extremity/TAPES-Upper, Research and Development-36/RAND-36, EQ-5D-5L, visual analogue scale/VAS, the Dutch version of the Quebec User Evaluation of Satisfaction with assistive technology/D-Quest, patient-reported outcome measure to assess the preferred usage features of upper limb prostheses/PUF-ULP) to compare user experiences and quality of life in the ICF-categories ‘Activities’, ‘Participation’, and ‘Environmental Factors’ (between-group comparisons).Results‘Body Function’ and ‘Activities’: nearly all users of MHPs had similar joint angle coordination patterns with an MHP as when they used an SHP. The RCRT in the upward direction was performed slower in the MHP condition compared to the SHP condition. No other differences in functionality were found. ‘Participation’: MHP users had a lower EQ-5D-5L utility score; experienced more pain or limitations due to pain (i.e., measured with the RAND-36). ‘Environmental Factors’: MHPs scored better than SHPs on the VAS-item holding/shaking hands. The SHP scored better than the MHP on five VAS-items (i.e., noise, grip force, vulnerability, putting clothes on, physical effort to control) and the PUF-ULP.ConclusionMHPs did not show relevant differences in outcomes compared to SHPs on any of the ICF-categories. This underlines the importance of carefully considering whether the MHP is the most suitable option for an individual taking into account the additional costs of MHPs.