4516 Background: Active surveillance (AS) is a commonly used strategy in patients (pts) with low tumor burden or slow growing disease. However, few studies have assessed AS for mRCC compared to immediate treatment. We aimed to assess the outcomes and safety of AS in comparison to immediate systemic treatment for mRCC pts. Methods: Using CKCis, mRCC pts diagnosed between January 1, 2011 and December 31, 2016 were identified. AS strategy was defined as: (1) start of systemic therapy ≥6 months after diagnosis of mRCC; or (2) never receiving systemic therapy for mRCC with an overall survival (OS) ≥1 yr (OS ≥ 1 yr a surrogate to exclude pts not started on treatment due to poor prognosis). Pts starting systemic treatment < 6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until 1^st line treatment failure (TTF) between the two cohorts were compared. Results: A total of 863 pts met criteria for AS (cohort A). Of these, 370 started treatment ≥ 6 months after their initial diagnosis (cohort A1) and 493 never received systemic treatment and were alive for ≥1 year (cohort A2). 848 pts received immediate systemic treatment (cohort B). Median age for pts in cohort A and B was 65.1 (19.0-91.5) vs. 62.2 yrs (23.1-87.1) (p < 0.0001). Sex distribution was not statistically different. Pts in cohort A had fewer sites of metastatic disease vs. cohort B ( < 0.0001) and 23% of pts in cohort A had metastasectomy vs. 5% in cohort B (P = < 0.0001). Five-year OS probability was significantly greater for cohort A than for cohort B (70.2% vs. 32.1%; P < 0.0001). After adjusting for IMDC risk criteria and age, both OS (HR 0.46, 0.38-0.56, P < 0.0001) and TTF (HR 0.79, 0.69-0.92, P = 0.0021) were greater in cohort A1 vs. B. For cohort A1 the median time on AS was 14.2 m (range 6 – 71). Conclusions: Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of pts may be safely observed without immediate initiation of systemic therapy. Prospective validation is required in the contemporary immunotherapy era.