OBJECTIVES: A single MitraClip implant is often considered enough to achieve adequate mitral regurgitation (MR) reduction. The aim of this study was to compare MR recurrence in patients with an initial optimal result treated with a single clip versus those treated with two clips. METHODS: From October 2008 to May 2016, 322 patients were treated with the MitraClip procedure at our institution. We retrospectively selected all patients treated for functional MR (FMR) and degenerative MR (DMR) aetiologies with residual MR ≤ 1+, excluding patients who required > 2 clips. FMR and DMR were analysed separately. RESULTS: In FMR, a single clip was used in 45 patients and 2 clips in 99 patients. The single clip group had smaller coaptation depth (1.1 ± 0.3 vs 1.3 ± 0.3 mm, P = 0.022) and jet extension (10.5 ± 2.1 vs 13.0 ± 3.6 mm, P = 0.026) as well as left ventricular end-diastolic diameter (64.4 ± 7.3 vs 69.0 ± 7.9 mm, P = 0.001). Freedom from MR≥3+ after 4 years was 71.9 ± 8.9% in patients receiving a single clip vs 88.0 ± 5.2% in those receiving 2 clips, single clip use being an independent predictor of MR recurrence (HR 3.48, CI 1.24-9.81, P = 0.018). In DMR, a single clip was deployed in 24 patients and 2 clips in 30 patients. The single clip group had a smaller flail gap (3.6 ± 0.7 vs 6.8 ± 2.5, P = 0.002). Freedom from MR≥3+ after 2 years was 82.5 ± 8% in patients with a single clip vs 100% in those with 2 clips, P = 0.014. The residual mitral area was reduced in patients with 2 clips compared with those with single clip, both in FMR (P = 0.015) and DMR (P = 0.039), but it was not associated with increased death rate during the follow-up period (all P > 0.05). CONCLUSIONS: Despite favourable anatomical characteristics and an optimal initial result, implantation of a single clip was associated with an increased recurrence of MR compared with that of 2 clips, both in FMR and in DMR. Caution should be exercised with the implantation of a single clip. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.