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Purpose: To investigate the costs, quality of life, and user experiences associated with upper limb prosthesis use, and to evaluate the cost-effectiveness of multi-grip compared to standard myoelectric hand prostheses (MHPs/SHPs). Materials and methods: The EQ-5D-5L to assess the quality of life, the patient-reported outcome measure to assess the preferred usage features of upper limb prosthesis (PUF-ULP), and a cost questionnaire (societal perspective) were completed by 242 prosthesis users (57% men; mean age = 58 years). Incremental cost-utility and cost-effectiveness ratios (ICUR/ICER) with respectively the EQ-5D-5L and PUFULP were calculated to compare MHPs with SHPs. Statistical uncertainty was estimated using bootstrapping. Netherlands Trial Registry number: NL7682. Results: The mean yearly total costs related to prosthesis use of MHPs (e54 112) and SHPs (e23 501) were higher compared to prostheses with tools/accessories (e11 977), body-powered (e11 298), and cosmetic/passive prostheses (e10 132). EQ-5D-5L and PUF-ULP scores did not differ between prosthesis types. ICUR was e-728 833 per quality-adjusted life year; ICER was e-187 798 per PUF-ULP point gained. Conclusions: Myoelectric prostheses, especially MHPs, were most expensive compared to other prostheses, while no differences in quality of life and user experiences were apparent. MHPs were not cost-effective compared to SHPs. When prescribing MHPs, careful consideration of advantages over SHPs is recommended. [ABSTRACT FROM AUTHOR]