OBJECTIVES: To examine AE rates and associated costs among mCRC patients treated with bevacizumab (BV) or cetuximab (CET). METHODS: Using a large national US claims database from 1/2008-3/2012, patients with mCRC were identified (≥2 claims for colon or rectal cancer and metastatic disease), with enrollment in the health plan for ≥6m before and after the 1^st metastatic claim date.  Patients received BV or CET during  1^st line (LOT1) and/or 2^ndline (LOT2) therapy. LOT2 was defined as addition of any new agent ≥28d after start of LOT1. AEs, identified with ICD-9 codes on healthcare claims, were assessed from start of 1st targeted therapy in LOT1 or LOT2 to the last targeted therapy date+28d or a new LOT. Incident Rate Ratios (IRR) were calculated for each AE (incidence rate for CET/incidence rate for BV). Multivariate regression analyses assessed medical costs. RESULTS: In LOT1, there were 1,255 BV and 119 CET patients; in LOT2, 671 BV and 157 CET patients. The CET cohort had higher incidence rates (IRR>1; p<0.05) in LOT1 for: dermatologic events (IRR=8.67), GI (IRR=1.38), DVT (IRR=2.58), metabolism (IRR=2.11), hemorrhage (IRR=2.32) and infusion reactions (IRR=1.81). In LOT2, the CET cohort had higher rates (p<0.05) for: dermatologic (IRR=9.28), GI (IRR=1.36), DVT (IRR=1.75), metabolism (IRR=1.75), infusion reactions (IRR=1.54), hemorrhage (IRR=2.32); and Sepsis (IRR=2.68); BV had higher proteinuria (IRR=0.64; p<0.01). GI perforation incidence rates trended higher (p>0.05) with BV (LOT1:0.02 vs. 0; LOT2:0.001 vs. 0).  BV patients had lower per-patient per-month (PPPM) total costs (LOT1 adj. difference: –$4,202, p<0.01; LOT2: -$3,776, p=0.01), and PPPM AE medical costs (LOT1:-$5,851, p<0.01; LOT2: –$4,293, p=0.02). CONCLUSIONS: BV during first or second line mCRC treatment was associated with lower AE rates and lower PPPM costs compared to CET. Limitations include the inability to distinguish events related to targeted vs. chemo agents and high baseline rates of certain events (e.g., hypertension).