Purpose: The aim of the study was to investigate the effectiveness of the postoperative 12-month exercise program compared to usual care on disability and health-related quality of life (HRQoL) in patients after lumbar spine fusion surgery (LSF). Methods: Altogether, 98 patients with isthmic (31) or degenerative (67) spondylolisthesis were randomised to exercise therapy group (EG) (n = 48) or usual care group (UCG) (n = 50) 3 months after LSF. EG patients had home-based progressive strength and aerobic training program for 12 months. UCG patients received only oral and written instructions of exercises. Oswestry Disability Index (ODI) and HRQoL (RAND-36) were evaluated at the time of randomization, at the end of the intervention and 1 year after intervention. Results: The mean ODI score decreased from 24 (12) to 18 (14) in the EG and from 18 (12) to 13 (11) in the UCG during intervention (between-groups p = 0.69). At 1-year follow-up, 25 % of the EG and 28 % of the UCG had an ODI score ≥20. No between-group differences in HRQoL change were found at any time point. The mean (95 % CI) physical functioning dimension of the HRQoL improved by 10.0 (4.6–15.3) in the EG and by 7.8 (2.5–13.0) in the UCG. In addition, the role physical score improved by 20.0 (7.7–32.3) in the EG and by 16.4 (4.4–28.4) in the UCG during the intervention. Conclusions: The exercise intervention did not have an impact on disability or HRQoL beyond the improvement achieved by usual care. However, disability remained at least moderate in considerable proportion of patients.