Objective: While bisphosphonates have been available for many years, new drugs in this class have recently become available. We sought to understand whether differences exist on fracture risk and adverse events among oral (i.e., alendronate, risedronate, ibandronate) and intravenous (i.e., ibandronate, pamidronate, and zoledronic acid) bisphosphonates available in the United States in postmenopausal women. Methods: A search of the English-language literature in Medline and Cochrane databases was conducted from 1997 to 2007 using combinations of these search terms: bisphosphonates, alendronate, risedronate, zoledronic acid, pamidronate, ibandronate, fracture, adverse events, and osteoporosis. Articles were included if they were meta-analyses or randomized controlled trials (RCT) and provided information on fracture risk and adverse events. Results: In the most recent meta-analysis, alendronate (n=12,099 patients; 11 trials) and risedronate (n=13,795 patients; 6 trials) reduced the risk of vertebral fractures (RR:0.55, 95%CI 0.45-0.67; RR:0.61, 95%CI 0.50-0.76) and non-vertebral fractures (RR:0.84, 95%CI 0.74-0.94; RR:0.80, 95%CI 0.72-0.90), including hip fractures (RR:0.61, 95%CI 0.40-0.92; RR:0.74, 95%CI 0.59-0.94). Similarly, in a RCT among 7765 women, the incidence of vertebral fractures, non-vertebral, and hip fractures was significantly reduced with zoledronic acid (RR:0.30, 95%CI 0.24-0.38; RR:0.75, 95%CI 0.64-0.87; RR:0.59, 95%CI 0.42-0.83). In contrast, oral ibandronate (n=1952) lowered the risk of vertebral fractures (RR:0.62, 95%CI 0.41-0.75) but not nonvertebral fractures. Data on fracture risk with pamidronate were not identified. Adverse events were similar between bisphosphonates and placebo in all included studies, except with zoledronic acid where serious atrial fibrillation (1.3% vs. 0.5%;p<0.001), an increase in Scr >0.5mg/dL (1.2% vs. 0.4%;p=0.001), and urinary protein >2+ (0.5% vs. 0.2%;p=0.06) were higher with treatment compared to placebo. Conclusion: This evidenced-based literature review shows that clinical differences among bisphosphonates exist. This suggests that selection of bisphosphonates needs to be individualized to maximize the desired effect and minimize risks.