Purpose: The aim of this study was to evaluate work ability, activity limitations and physical activity in adults that had gone through major bone sarcoma resection and reconstruction surgery in hip and knee. Materials and methods: Twenty patients, of 72 enrolled, and 20 controls were included in this cross-sectional study. Work Ability Index scores (general [0–10 points], physical and mental [1–5 points]), the Patient Specific Functional Scale (0–10 points), step counts and the International Physical Activity Questionnaire (IPAQ) were assessed. Adjusted and unadjusted general linear models were applied. Results: The patients had a mean age of 43 (range, 20–71) years and were assessed 7 years (range, 2–12) after surgery (proximal femoral n = 9, distal femoral n = 7, proximal tibia n = 4). Compared with controls, patients had lower general work ability (mean difference [95%CI], −1.3 points [−2.1, −0.5]) and work ability in relation to physical demands at work (−1.4 points [−2.0, −0.8]). The patients reported higher severities of activity limitation (−6.7 points [−7.9, −5.4]). There were no between-group differences in step counts or IPAQ-scores. Conclusion: Despite similar levels of physical activity, patients showed poorer work ability and severe activity limitation. Post-operative rehabilitation in patients of the working-age population should include assessments of work ability and activities important to the individual.IMPLICATIONS FOR REHABILITATION Adults that have gone through resection and reconstruction surgery following bone sarcoma in lower extremity show clinically relevant reductions in work ability and self-selected activities To tailor post-operative rehabilitation at short and long term, initial assessment and monitoring should include work ability and activities important to the individual patient.