Safety and treatment patterns of sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) had been previously reported using retrospective chart review of patients treated in US tertiary centers. Because practice patterns may vary between hospital- and office-based settings, this study examined safety and treatment patterns of these agents in US community oncology clinics. Medical records were retrospectively reviewed for 250 patients with mRCC treated at 18 community oncology clinics. Eligible patients were ≥18 years old and received ≥1 prescription for sunitinib (n = 131) or sorafenib (n = 119) as first-line anti-angiogenic treatment. Rates of adverse events (AEs) and treatment modifications were analyzed; reasons for treatment modifications were examined. Median duration of first-line sunitinib and sorafenib treatment was 5.9 and 5.5 months, respectively. Among patients treated with sunitinib and sorafenib, 86% (30%) and 87% (28%), respectively, experienced ≥1 all-grade (grade 3/4) AE. The most common AEs were fatigue/weakness in sunitinib (all-grade: 42%; grade 3/4: 5%) and skin rash in sorafenib (all-grade: 35%; grade 3/4: 6%). Sixty-two and 64% of patients treated with sunitinib and sorafenib, respectively, had ≥1 treatment modification due to AEs. Recorded AE rates in patients with mRCC treated with angiogenesis inhibitors in community practice tended to be lower than in tertiary centers, possibly due to shorter treatment duration. Rates of treatment modifications due to AEs tended to be higher in community practice. This study provides evidence from an office-based setting of unmet need for agents that may provide improved tolerability in mRCC.