Purpose <p>The Back At work After Surgery (BAAS) care pathway integrates medical and occupational care to enhance return to work (RTW) after knee arthroplasty (KA). BAAS has shown effectiveness in improving RTW outcomes, but its economic impact is unknown. This study evaluates the costs and return on investment (ROI) of BAAS compared with care-as-usual.</p> Methods <p>This multicenter, prospective cohort study involved 270 employed patients having KA, comparing the BAAS pathway (<i>n</i> = 137) to care-as-usual (ACTIVE trial, <i>n</i> = 133). The ROI was evaluated from societal and employer’s perspectives. Productivity (absenteeism and presenteeism) and healthcare (primary and secondary) costs were assessed using cost questionnaires administered at 3, 6, 9, and 12 months post-surgery. Propensity score matching and multiple imputation addressed non-randomization and missing data, respectively. ROI was calculated by dividing the netto benefits—defined as reductions in productivity and healthcare costs, or productivity costs alone minus costs of the BAAS intervention—by the intervention costs multiplied by 100%.</p> Results <p>Propensity score-matched analyses included 102 patients per cohort. The total netto benefits from employers and societal perspective were of €4,493 and €4,982, respectively. Intervention costs were €845/patient. This resulted in a ROI of 590% (95% CI 67–1112%) and 532% (95% CI 27–1037%) from the societal and employer’s perspective, respectively, per Euro invested.</p> Conclusions <p>The BAAS care pathway demonstrates a favorable economic impact through significant 12 month downstream reductions in absenteeism and healthcare costs, and a positive ROI from both the societal and employer perspective.</p> <p><i>Trail registration</i><b>:</b> This study was retrospectively registered at clinicaltrails.gov (<a href="https://clinicaltrials.gov/ct2/show/NCT05690347">https://clinicaltrials.gov/ct2/show/NCT05690347</a>, date of first registration: 19-01-2023).</p>