Background: Wrist immobilization orthosis is a commonly adopted treatment method for wrist regarding pathologies. In recent years, a group of 3D-printed immobilization orthosis for the upper extremity has been proposed. However, they were mainly developed as substitutes for traditional casts for the upper extremity for short-term usage. There has been no definite attempt to design 3D-printed orthosis to immobilize the upper extremity used as an assistive device for long-term usage. Objective: Develop a patient-specific orthosis for wrist immobilization in long-term usage, which has suitable functionality, the comfort of wearing, and an efficient fabrication process by exploiting the benefits of Additive Manufacturing technology. Methods: Structure concepts were generated by modes of donning and doffing and evaluated with criteria. The prototype was assessed together with an orthopedic technician. For the next, the prototype was validated with actual patients who were suffering from degenerative wrist pathologies. The subjects wore their wrist immobilization orthosis for two months and were asked about their experiences. Results: In total, eleven wrist immobilization orthosis prototypes were validated with five subjects (two males and three females) suffering from degenerative wrist pathologies (Rheumatoid Arthritis: one subject, Osteoarthritis: three subjects, and Ehlers-Danlos syndrome: one subject). 45 % of prototypes provided excessive pressure on bony prominences. Around 55 % of prototypes caused unacceptable pain at distal palmar creases. Specifically, the movement of putting it on and off brought complications for 91 % of all prototypes. For three subjects who could use their orthoses for two months, the orthoses functioned well, decreasing pains in the wrist while having daily activities. Conclusion: First, the structure of the wrist immobilization orthosis was well-designed, performing proper support during activities of daily living. Second, the comfort evaluation was conditionally positive; due to the rigid hardness of the material, two out of eleven orthoses were too painful to wear for the further test. Since the morphology of bony eminences and the amount of the cutaneous fats around those areas are dissimilar for all people, it was hard to design pain-zero orthosis for two subjects. Lastly, SLS printing with PA12 material offered apparent advantages over traditional fabrication methods. All works were conducted digitally from the scanning to fabrication, and there was no waste of materials. Despite six working days of delivery time from the outsourcing company, the orthosis did not require any labor-intensive procedures.