Background. The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I–III) breast cancer. Materials and Methods.We performed a systematic review andmeta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, andmajor cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatmentwith zoledronic acid versusnonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedureswereused toanalyze the studyoutcomes. Results.Fifteenstudieswereconsideredeligibleandwere further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70–0.94). No significant differenceswere found for the disease-free survival outcome (seven studies, 7,541 patients;HR,0.86;95%CI,0.70–1.06)or incidenceofbonemetastases(sevenstudies,7,543patients;oddsratio[OR],0.94;95%CI, 0.64–1.37). Treatmentwith zoledronic acid led to a significantly loweroverall fracture rate (OR, 0.78; 95%CI, 0.63–0.96). Finally, the rateofosteonecrosis of the jawwas0.52%. Conclusion. Zoledronic acid as adjuvant therapy inbreast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment. The Oncologist2013;18:353–361 Implications for Practice: Zoledronic acid appears to have a role in adjuvant therapy in patients with breast cancer because it reduces the fracture rate and seems to offer survival benefits. The need for additional research is essential to determine if its effect is enhanced in low-estrogen environments and to reveal the magnitude of interaction between estrogen levels and zoledronic acid.Meanwhile, in patients with signs of bone loss (osteopenia or osteoporosis) during adjuvant endocrine therapywhen the initiation of bisphosphonates is indicated, zoledronic acidmight be preferred over other therapies due to its beneficial effect on survival.