OBJECTIVE: Knowledge about the effects of exercise in severe and endstage osteoarthritis (OA) is limited. The aim was to evaluate the efficacy of a neuromuscular exercise program in patients with clinically severe hip or knee OA. METHODS: This was a randomized controlled assessor-blinded trial. Patients received an educational package (care-as-usual) only, or care-as-usual plus an 8-week neuromuscular exercise intervention (NEMEX-TJR). NEMEX-TJR was supervised by a physiotherapist, twice weekly for 1 h. The primary outcome was Activities of Daily Living (ADL) subscale from the Hip disability and Osteoarthritis Outcome Score (HOOS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. The secondary outcomes were the HOOS/KOOS subscales Pain, Symptoms, Sport and Recreation, and Joint-related Quality of Life. Exploratory outcomes were functional performance measures and lower limb muscle power. RESULTS: Included were 165 patients, 56% female, average age 67 years (SD ± 8), and a body mass index of 30 (SD ± 5), who were scheduled for primary hip or knee replacement. The postintervention difference between mean changes in ADL was 7.2 points (95% CI 3.5 to 10.9, p = 0.0002) in favor of NEMEX-TJR compared with control. Second, there were statistically significant differences between groups in favor of NEMEX-TJR on all self-reported outcomes and most functional performance tests (walk, chair stands, and 1-leg knee bends). Stratified analyses according to joint revealed moderate effect size for ADL for hip patients (0.63, 95% CI 0.26 to 1.00). Corresponding effect size for knee patients was small (0.23 95% CI -0.14 to 0.60). CONCLUSION: Feasibility of neuromuscular exercise was confirmed in patients about to have total joint replacement. Self-reported activities of daily living and objective performance were improved and pain reduced immediately following 8 weeks of neuromuscular exercise. While the effects were moderate in hip OA, they were only small in knee OA. ClinicalTrials.gov Identifier: NCT01003756.