Background and Objectives. Chronic graft-versus-host disease (GVHD) remains the most common late complication of allogeneic stem cell-transplantation, producing significant long-term morbidity and contributing to a substantial risk of late mortality. Chronic GVHD may be more common, more protracted and less responsive to current treatments after,peripheral-blood stem cell (PBSC) transplantation than after bone marrow transplantation. The purpose of this retrospective cohort study was to determine whether the hazard of extensive chronic GVHD after allogeneic PBSC transplantation could be decreased by prolonging cyclosporine A (CsA) prophylaxis !, over 12 months. Design and Methods. Fifty-seven consecutive patients with hematologic malignancies who had received a PBSC transplant from an HLA-identical sibling were evaluable for chronic GVHD. All patients began CsA tapering at day 50 but 2 different durations of immunosuppression were used: the first 36 patients were allocated to receive a 6-month course with tapering by 5% at Weekly intervals (group A), while the following 21 received a 12-month course with tapering by 5% every,2 weeks (group B). Results. The cumulative incidence of extensive chronic GVHD at 2 years was 69% (95% CI; 53-85%) for group A and 25% (95%-CI, 3-47%) for group B with a significantly lower hazard in group B than in group A (HR=0.2; 95% CI, 0.07-0.57; p=0.0009). In multivariate analysis, the 12-month CsA tapering schedule was associated with a significantly decreased risk of extensive chronic GVHD (HR=0.2; 95% CI; 0.06-0.66; p=0.008,). The hazard of transplant-related mortality, relapse and failure to survive in remission was not significantly different among the 2 groups. Interpretation and Conclusions. One-year CsA prophylaxis seems to be more effective than the standard six-month transplant from an HLA=identical sibling. Conclusive assessment of the benefits of such prolonged immunosuppression; in terms of better quality of life-and minor morbidity, requires both long-term follow-up to; evaluate the rates of relapse and secondary tumors and a randomized setting.