The creation of fistulas or grafts before starting dialysis is recommended, but whether it reduces major adverse events is largely unknown. The objective of this study was to determine if early access creation was associated with a reduced risk of hospitalization from sepsis and mortality. Fistulas or grafts created at least 4 mo before starting hemodialysis were defined as Early creations (n = 1240), and accesses created between 4 mo and 1 mo before starting hemodialysis were defined as Just Prior creations (n = 997). Accesses created within 1 mo of starting dialysis or after were defined as Late creations (reference group, n = 3687). Hemodialysis catheter use was defined as insertion, removal, or manipulation of a catheter before the occurrence of sepsis. Eighty percent of accesses were fistulas. Early access creation was associated with a relative risk (RR) of sepsis of 0.57 (95% CI, 0.41 to 0.79) compared with Late access creation. Catheter use increased the risk of sepsis by 1.41 (95% CI, 1.14 to 1.81). The risk of sepsis with Early creation decreased to 0.48 (95% CI, 0.35 to 0.65) if catheter use was not adjusted. Early access creation was associated with lower mortality (RR 0.76; 95% CI 0.58 to 1.00), but this association became nonsignificant if catheter use and sepsis were adjusted. Catheter use and sepsis independently increased mortality. This study demonstrates that fistula creation at least 4 mo before starting chronic hemodialysis is associated the lowest risk of sepsis and death, primarily by reducing the use of hemodialysis catheters.