Buttonhole (constant site) cannulation has emerged as an attractive technique for needling arteriovenous fistulae. However, the balance of benefits and harms associated with this intervention is unclear. We conducted a systematic review of studies reporting outcomes with buttonhole cannulation. The setting and population included adult patients receiving home or center hemodialysis. We searched MEDLINE, Embase (1980-June 2012), and CINAHL (1997-June 2012), for randomized and observational studies. We also searched conference proceedings (2009–2011). The interventions included: 1) buttonhole cannulation established by sharp needles, with or without a polycarbonate peg, 2) rope-ladder cannulation. Outcomes of interest included: Facility practices, systemic infection, local infection, access survival, access interventions, access-related hospitalization, patient survival, pain, quality of life, and aneurysm formation. We identified 23 full-text articles and 4 abstracts; 3 were open-label trials, and the remainder observational studies of varying design and methodological quality. Studies were predominantly descriptive and lacked direct comparisons between buttonhole and rope-ladder cannulation. No qualitative differences in outcomes were noted among home and center hemodialysis patients using buttonhole cannulation. Rates of bacteremia were generally higher with buttonhole cannulation. Studies reporting access survival, hospitalization, quality of life, pain, and aneurysm formation had serious methodological limitations that limited our confidence in their estimates of effect. Among the various facility practices that were described, only the application of mupirocin cream was noted to be associated with reduced risk of infection. Limitations in included studies were short follow-up, crossover designs, lack of parallel control groups, and the use of patient-reported outcome measures that were not well validated. The main limitation of this review was a limited literature search. Buttonhole cannulation may be associated with an increased risk of infection. Larger, more definitive studies are needed to determine whether this technique is safe for broader use.