Background: Pazopanib is an oral tyrosine kinase inhibitor and is currently approved for treatment of patients with advanced or mRCC in the first-line, or second-line setting, after progression on cytokine therapy. No reports of efficacy and safety are available post targeted therapy. We conducted a retrospective analysis of cases receiving pazopanib after failure of other targeted agents. Methods: The study was reviewed and approved by our Institutional Review Board. Review of medical records of advanced renal cancer patients, treated with second-line pazopanib from April 2010 to August 2011 at Karmanos Cancer Center was performed. The Common Terminology Criteria for Adverse Events version 4.0 was used to grade the severity of definitely treatment-related adverse events (AEs). Results: 14 patients are included to date in this ongoing data collection and analysis study. Median age was 58 years, 8 were Caucasian, 4 African American, and 2 other races. By the MSKCC criteria, 1 patient was favorable, 6 were intermediate and 7 poor risk. Pazopanib was utilized as second line in 4 patients, third line in 5, and even later in 5. Prior line targeted therapies included sunitinib (8), temsirolimus (9), everolimus (4), sorafenib (1), bevacizumab (1) and axitinib (1). Nine of 14 patients to date were treated with pazopanib for at least 2 months and were assessed for response by imaging studies. One achieved partial remission; 5 had stable disease, and 3 had progression. The median time to progression after starting pazopanib was 4.0 months. The predominant AEs were grade 1 or 2, which included fatigue (4), liver enzyme elevation (3), diarrhea (2), hypertension (2), skin rash (1), depression (1) and hyponatremia (1). No grade 3 or 4 AEs, or definitely treatment-related deaths were observed. Conclusions: Pazopanib appears to maintain efficacy and tolerability in mRCC even after failure of other targeted therapies. Further investigations of larger patient cohorts in this setting are recommended.