We investigated the toxicity and efficacy of early administration of bortezomib in 14 patients with residual disease (n=9) or complete remission (immunofixation-negative) (n=5) after a median of 383 days (range, 47–1317) after melphalan/fludarabine-based dose-reduced allogeneic SCT for multiple myeloma. The median age was 49 years (range, 32–62), and stem cell graft was from HLA-identical siblings (n=2) or unrelated donors (n=12). Three patients had received prior Thalidomide and donor lymphocyte infusion, and 2 of them still received low dose thalidomide (50 mg) during bortezomib treatment. The study consisted of two cycles bortezomib (1.3 mg/m2) given intravenously on day 1, 4, 8 and 14 (q21d). In case of response and low toxicity, two further cycles were applied. Eleven patients completed two cycles, and 4 patients completed four cycles. Two patients stopped after three cycles due to side-effects; 3 patients could not complete the proposed two cycles and stopped either after the first injection (n=1) of the first cycle, or after the second (n=1) or third (n=1) injection of the second cycle due to neurotoxicity. Major toxicity was thrombocytopenia grade IV (> 75 % reduction) which was seen in 6 patients (43 %), but none required platelet support. Neutropenia grade IV was seen in 2 patients (14 %), neurotoxicity grade III and IV was observed in 3 patients (21 %) while mild grade I-II neuropathy was seen in 10 patients (71 %). Other toxicity was fatigue grade I (85 %), nausea grade I (50 %), diarrhea grade I-II (93 %). Two patients with acute or chronic GvHD of the skin experienced deterioration of the manifestation, which could be treated succesfully with corticosteroids. A significant decrease during bortezomib-therapy was observed for CD3+ cells (p=0.02), while no effect was seen for B-cells (CD19+) (p=0.4). Two patients who received bortezomib on day 125 and 201 after allogeneic SCT experienced Herpes zoster infection during and 2 weeks after bortezomib treatment, respectively. All 9 patients with persistent disease showed further regression of the paraprotein including negative immunofixation in 5 patients. We conclude that early bortezomib after allogeneic SCT for patients with multiple myeloma is active and can induce further regression of the paraprotein. The toxicity is considerable especially if given early after allo SCT.