Background: Approximately 20- 30 % of the patients (pts) with renal cell carcinoma (RCC) develop recurrence after treatment of localized disease. Of these pts, the great majority recur within the first few years following surgery. Rarely, late recurrences (LRs) are seen after >5 years of disease free survival. Targeted therapies (TT) have improved the outcome in patients (pts) with metastatic renal cell carcinoma (mRCC). Little data is available about outcomes of mRCC pts with LR treated with TT. Methods: We reviewed records of consecutive pts with mRCC who had LR >5 years and were treated with TT between 11/1/2006 and 11/1/2013. Outcomes were tabulated using basic statistical techniques. Adverse Events (AEs) were graded using CTCAE v4.0 Results: 25 pts (median age 69 years, 84% male, 100% clear-cell, all with prior nephrectomies) met inclusion criteria with LR>5 years. 16% had Karnofsky PS<80%. 76% had good-risk disease and 24% had intermediate-risk by MSKCC criteria at time of diagnosis with recurrent disease. 11 pts died. Median OS for all pts from the time of recurrence is 27.9 mos (range 6.7 – 129 mos). The 3 year OS rate from time of recurrence was 52%. The median number of sequential TT received was 2 (range 1-4). Median time on first line TT was 20.7 months; median time on all TT was 35.1 months. 41% of pts received pazopanib in the frontline setting, 26% received sunitnib, 26% received sorafenib and 7% received other TT. 68% received TT in the second-line and subsequent settings. Common AEs of TT included fatigue (52%), diarrhea (36%), hypertension (36%), anorexia (28%), hair and skin changes (24%), increased LFTs (20%), nausea/vomiting (16%), and 95% of AEs were grade 1/2. Conclusions: In this retrospective study, the outcomes of mRCC pts with LR treated with TT appears improved. Pts had overall survival compared to historical controls, but total time on TT and three year OS rate were prolonged. AEs were mild/moderate and manageable. Outcome data on different sequences of TT will be provided at meeting presentation.