Background: Frequent hemodialysis (HD) may be associated with an increased risk of vascular access complications. Studies addressing vascular access outcomes in frequent HD show conflicting results. Methods: We searched Medline for trials looking at vascular access outcomes in frequent HD. Results: Nineteen studies met the inclusion criteria; only studies with a control group were included for analysis (n = 15). The vascular access event rate was higher in intensive HD as compared to conventional HD (difference of 6.7 events per 100 patient-years, p = 0.009). Overall event rates were not significantly different between conventional and intensive HD when stratified for access type, but were notably higher in the arteriovenous grafts and catheter group as compared to the arteriovenous fistula (AVF) group. Conclusion: Intensive HD is associated with an increased risk of vascular access complications. Overall reported event rates were lower in the AVF group. Further controlled studies should investigate whether a ‘fistula first' strategy may be recommended also for intensive HD.