Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of <60 and ≥60 ml/minute were similar. Although there was a tendency for shorter overall survival along lower estimated glomerular filtration rates, this difference did not reach a statistical significance. Overall and severe adverse events, and dose modification and treatment discontinuation rates were higher in patients with renal impairment. Patients with renal failure had more thrombocytopenia and diarrhea. While thrombocytopenia was mild to moderate and manageable, diarrhea, which led to serious adverse events, was more severe in patients with renal failure who received bortezomib as monotherapy. Bortezomib appears to be active; however, when used alone, it may cause more frequent and severe adverse events in patients with MM and renal failure.