Osteoarthritis (OA) of the trapeziometacarpal joint (TMCJ) can be caused by biomechanical wear on the articular cartilage due to high joint contact pressure, leading to severe pain in the thumb. Static orthoses have been applied for treatment in the early stages of OA to immobilize the TMCJ in the comfortable posture without considering contact pressure at the TMCJ, resulting in a high failure rate of pain relief during splinting. To ensure successful treatment, it is desirable to immobilize the TMCJ in an optimal posture that minimizes biomechanical joint contact pressure. This paper presents a patient-specific TMCJ orthosis design for the optimal posture, based on joint contact pressure obtained from a computed tomography (CT) image-based finite element (FE) TMCJ model. The estimated pressure at the subject-specific optimal posture averaged 2.8E-3 MPa, which was lower compared to the average pressure of 3.2E-2 MPa at the non-optimal but comfortable posture. To maintain this subject-specific optimal TMCJ posture, the orthosis was designed based on individual hand geometries with three-dimensional (3D) printing technology. The 3D-printed orthosis was preliminarily evaluated by patients with moderate to severe OA, and all patients reported pain relief. The Visual Analog Scale (VAS) and Disabilities of Arm, Shoulder, and Hand (DASH) scores improved by 1.8  1.7 and 13.1  5.4, respectively. For orthotic treatment in clinics, the FE model-based TMCJ orthosis design for the subject-specific optimal posture is beneficial in achieving relief of pain caused by OA.