Background: BM are frequently present in patients with mRCC. BM cause significant morbidity and are associated with high rates of skeletal related events (SREs). The purpose of this retrospective analysis was to assess the impact of BM and BIS use on outcomes including progression-free survival (PFS) and overall survival (OS) in patients with mRCC. Methods: We conducted a pooled analysis of patients with mRCC treated from 2003-2011 on phase III (NCT00083899, NCT00065468, NCT00678392) and phase II trials (NCT00054886, NCT00077974, NCT00083889, NCT00338884, NCT00137423). Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results: We identified 2,749 patients treated with sunitinib (n=1,059), sorafenib (n=335), axitinib (n=359), temsirolimus (TEM) (n=208), TEM + interferon-alfa (IFN) (n=208), or IFN (n=560). Most patients were male (71%), had baseline ECOG PS of 0 (47%) or 1 (51%), clear cell histology (91%), and prior nephrectomy (84%). 285 patients (10.4%) received treatment with BIS (zoledronic acid n=233, pamidronate n=57, unspecified n=1). No patients received denosumab. Of the 2,504 patients with data regarding site of metastasis at diagnosis, 31.9% (n=781) had BM. The rate of SREs in patients with BM compared to patients without BM was 6.4% versus 1.4% (p<0.0001). Presence of BM was associated with shorter PFS (5.1 vs. 6.7 months (mo), HR 1.195, 95% CI 1.076-1.328, p<0.0008) and OS (13.2 vs. 20.2 mo, HR 1.292, 95% CI 1.145-1.456, p<0.0001) when compared to those without BM. In patients with BM, the use of BIS was not associated with improved PFS (5.1 vs. 4.9 mo, HR 0.867, 95% CI 0.704-1.067, p=0.1785) or OS (13.3 vs. 13.1 mo, HR 0.904, 95% CI 0.722-1.132, p=0.3801) when compared to patients who did not receive BIS. In patients with BM stratified by type of first-line MTA (TKI, mTOR inhibitor, or IFN-based), use of BIS was not associated with improved PFS or OS. Conclusions: In this analysis, we confirm that the presence of BM is an adverse risk factor for shorter PFS and OS in patients with mRCC treated with MTAs. Treatment with BIS did not have a positive impact on survival in this cohort.