A number of medications promote the development of calcium pyrophosphate deposition disease (CPDD). We report 2 cases of acute CPDD after intravenous zoledronic acid therapy. Case #1: a 63-year-old female was admitted for vertebroplasty at the site of an osteoporotic fracture. She received an intravenous infusion of zoledronic acid 5mg on the day after the procedure. Acute CPDD developed in her right knee 24hours later. Findings from joint aspiration and standard radiography confirmed the diagnosis. Case #2: this 79-year-old woman had a history of CPDD was on glucocorticoid and hydroxychloroquine therapy for lupus. She was given an intravenous infusion of zoledronic acid 5mg as prophylaxis of glucocorticoid-induced osteoporosis. Joint pain and a fever developed later on the same day. After 5 days, she had arthritis of the right wrist, laboratory evidence of systemic inflammation, and hypocalcemia. Radiographs showed evidence of CPDD. A Medline search identified 6 cases of bisphosphonate-related CPDD, including 2 due to pamidronate, 2 to etidronate, 1 to alendronic acid, and 1 to neridronic acid. The features were similar to those in our patients, with a short time to onset, systemic inflammation in many cases, a tendency toward hypocalcemia, and radiographs that often showed evidence of CPDD. Bisphosphonate-induced CPDD is a rare eventuality that should nevertheless be borne in mind by rheumatologists. Also, in patients with CPDD while taking bisphosphonate therapy, a role for the drug in the symptoms should be considered.