Objective: To study the effectiveness of a 12-month exercise therapy on kinesiophobia and physical activity in patients with spondylolisthesis after lumbar spine fusion. Design: Randomized controlled trial. Subjects: Patients (n = 98) with spondylolisthesis who had undergone lumbar spine fusion. Methods: All patients (mean age 59 years) had received lumbar spine fusion surgery and identical postoperative instructions. Three months postoperatively, they were randomized into an exercise group (n = 48) or usual care group (n = 50). The exercise group received 12-month progressive home-based training with regular booster sessions, and the usual care group a single session of physiotherapy instruction. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK) and physical activity by the International Physical Activity Questionnaire (IPAQ) preoperatively, 3 months after lumbar spine fusion, and at the end of the 12-month intervention. Results: Before the intervention, the median (first quartile; third quartile) of TSK was 32.5 (29.0; 37.0) in the exercise group and 30.0 (25.8; 36.0) in the usual care group, changing to 30.0 (25; 36) in the exercise group and to 30.5 (24; 36.3) in the usual care group (between-group p = 0.17). IPAQ metabolic equivalent minutes per week increased from 1,863 (1,040; 3,042) to 3,190 (1,634; 6,485) in the exercise group and from 2,569 (1,501; 4,075) to 3,590 (1,634; 6,484) in the usual care group (between-group p = 0.92). Conclusion: Progressive 12-month home-exercise starting 3 months postoperatively was not superior to usual care in decreasing kinesiophobia or increasing physical activity in spondylolisthesis.