The PAD regime, composed of bortezomib, adriamycin and dexamethasone, improves the outcomes of patients with advanced multiple myeloma (MM), but at the same time produces high frequency of serious toxic side effects. For the first time, we evaluated the efficacy and safety of a bortezomib-dose-reduced PAD regime in the treatment of relapsed/refractory MM in this clinical study. Forty-five patients were treated with two to six 21-day cycles of PAD, comprising bortezomib at 1.3 mg/m(2) (P1AD, n = 21) or 1.0 mg/m(2) (P2AD, n = 24) (days 1, 4, 8, 11), adriamycin at 9 mg/m(2) (days 1-4) and dexamethasone at 40 mg/day (days 1-4). Overall, 36 patients (80 %) showed at least partial remission (PR), in which 9 cases (20 %) showed complete remission (CR) and 10 cases (22 %) showed very good partial remission (VGPR). The efficacy of PAD regimen in advanced MM patients was not related to the traditional prognostic factors. There was no significant difference between P1AD and P2AD in the rates of PR, CR or VGPR, 1.5-year progression-free survival (PFS), and overall survival (OS) (81 % vs. 79 %, 48 % vs. 38 %, 64 % vs. 59 %, and 85 % vs. 73 %, respectively). However, the grade 3-4 toxic effects, including thrombocytopenia (13 % vs. 38 %), peripheral neuropathy (8 % vs. 33 %) and 3-4 grade gastrointestinal reaction (13 % vs. 43 %), were markedly inhibited after P2AD compared to P1AD (P < 0.05). The bortezomib-dose-reduced PAD regime reduced the incidence of adverse reactions without affecting the treatment efficacy in patients with advanced MM.