Objective: Complications from skeletal-related events (SREs) constitute a challenge to the care of patients with bone metastasis originated from any type of malignancy. Our objective was to determine the reduction in morbidity (SREs) and mortality (overall) of clodronate, pamidronate, and zoledronic acid in patients diagnosed with bone metastasis. Methods: Medline and Embase (from inception to October 2007) were searched in order to retrieve randomized clinical trials evaluating targeted bisphosphonates in cancer patients with bone metastasis. Patients with a definite (i.e., biopsy-proven) diagnosis of metastatic bone disease were included in the analysis. We extracted and combined data from studies describing the number of patients reporting 12-month SREs and mortality data. Two independent reviewers identified articles, then extracted data; results were compared and settled through consensus. A random-effects meta-analytic model was applied in all calculations. Jadad's scale assessed study quality of reporting. Results: A total of 50 potential studies were identified. Thirty-five were excluded and 15 were evaluated. Quality of reporting of included studies was on average 59±24%. All three drugs showed beneficial effects in preventing all SREs over placebo in cancer patients with bone metastasis. Zoledronate was the pharmacological strategy reporting the lowest relative risk (RR=0.67; CI95%=0.55, 0.81; N=695), followed by pamidronate (RR=0.79; CI95%=0.71, 0.88, N=1951), and clodronate (RR=0.87; CI95%=0.75, 1.00; N=681). However, no clear advantage of one drug over the others was observed since confidence intervals overlapped substantially. All targeted bisphosphonates showed no benefits over placebo in reducing the number of deaths in a 12-month period (p>0.05). Conclusion: Clodronate, pamidronate, and zoledronate are able to reduce the morbidity of patients with bone metastasis in regards to SREs but not overall mortality.