The arteriovenous fistula (AVF) is the preferred hemodialysis access, but AVF-failure rate is high, and complications from AVF placement are rarely reported. There is no clear consensus on predictors of AVF patency. This study determined AVF outcomes and patency predictors at Mayo Clinic Rochester following the Fistula First Initiative. A retrospective cohort study of AVFs placed at Mayo Clinic from January 2006 through December 2008 was performed. The AVF placement-associated primary and secondary failure rates, complications, interventions, and hospitalizations were examined. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine primary and secondary patency and associated predictors. During this time frame, 317 AVFs were placed in 293 individual patients. The primary failure rate was 37.1% after excluding patients not initiated on hemodialysis during follow-up (n = 38) or those with indeterminate outcome (37 lost to follow-up; six died; two transplanted). Of usable AVFs, 11.4% later failed. AVF creation incurred complications and hospitalization in 21.2% and 12.3% of patients, respectively. The risk for reduced primary patency was increased by diabetes (HR, 1.54; 95% CI, 1.14 to 2.07); the risk for reduced primary and secondary patency was decreased with larger arteries (HR, 0.83; 95% CI, 0.73 to 0.94; and HR, 0.69; 95% CI, 0.56 to 0.84, respectively). Primary failure remains a major issue in the post-Fistula First era. Complications from AVF placement must be considered when planning AVF placement. Our data demonstrate that artery size is the main predictor of AVF patency.