The MitraClip procedure requires transseptal access of the left atrium with a 24F guiding sheath. We evaluated invasively whether a MitraClip induced iatrogenic atrial septal defect (IASD) leads to development of a relevant interatrial shunt and right ventricular overload. A total of 69 patients who underwent a MitraClip procedure due to a severe mitral valve regurgitation (MVR) were included in the observational, retrospective cohort study. All pressures were directly measured throughout the procedure. Cardiac index (CI), systemic (Qs) and pulmonary (Qp) flow were calculated using the Fick method. Successful MitraClip implantation increased CI (2.5±0.62 vs 3.05±0.77L/min/m2 ; P<.0001), whereas SVR (1491±474 vs 997±301dyns/cm5 ; P<.0001), PVR (226±121 vs 188±96dyn/s/cm5 ; P=.04), PCWP (23±6.1 vs 20±4.7mmHg; P=.0031), PA pressure (33.6±7.2 vs 31.9±6.6mmHg; P=.1437) and LA pressure (21.5±5.4 vs 18.7±4.9mmHg; P<.0001) all decreased. The effect on LA pressure was further enhanced by guiding catheter retrieval (14.4±4.6mmHg; P<.0001). At the end of the procedure, Qp (6.033±1.3L/min) exceeded Qs (5.537±1.3L/min) by 0.496L/min leading to a Qp:Qs ratio of 1.09 (P=.007). After 6months, echocardiography revealed no changes in RV diameter (42.96±6.95mm vs 43.81±7.67mm; P=.62) and TAPSE (17.13±3.33mm vs 17.36±3.24mm; P=.48). Our data show that the MitraClip procedure does not induce a relevant interatrial shunt or right ventricular overload. In fact, future studies will have to show whether the IASD may even be beneficial in selected patient populations by left atrial volume and pressure relief.