Background MitraClip implantation has emerged as a viable option in high surgical risk patients with severe mitral regurgitation (MR). We performed the present systematic review to assess the safety and efficacy of the MitraClip system for high surgical risk candidates with severe organic and/or functional MR. Methods Six electronic databases were searched for original published studies from January 2000 to March 2013. Two reviewers independently appraised studies, using a standard form, and extracted data on methodology, quality criteria, and outcome measures. All data were extracted and tabulated from the relevant articles' texts, tables, and figures and checked by another reviewer. Results Overall 111 publications were identified. After applying selection criteria and removing serial publications with accumulating number of patients or increased length of follow-up, 12 publications with the most complete dataset were included for quality appraisal and data extraction. All 12 studies were prospective observational studies. Immediate procedural success ranged from 72-100%; 30 day mortality ranged from 0-7.8%. There was a significant improvement in haemodynamic profile and functional status after implantation. One year survival ranged from 75-90%. No long term outcomes have been reported for high surgical risk patients. Conclusions MitraClip implantation is an option in managing selected high surgical risk patients with severe MR. The current evidence suggests that MitraClip can be implanted with reproducible safety and feasibility profile in this subgroup of patients. Further prospective trials with mid- to long-term follow-up are required.