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Background: Insufflation of carbon dioxide (CO2) into the operative field to prevent cerebral or myocardial damage by air embolism is a well known strategy in open-heart surgery. However, here is no general consensus on the best delivery approach.Methods: From January 2018 to November 2021, we retrospectively collected data of one hundred consecutive patients undergoing minimally invasive mitral valve repair (MIMVR). Of these, fifty patients were insufflated with continuous CO2 1 min before opening the left atrium and ended after its closure, and fifty patients were insufflated with one shot CO2 10 min before the start of left atrium closure. The primary outcome of the study was the incidence of transient post-operative cognitive disorder, in particular agitation and delirium at discontinuation of anesthesia, mechanical ventilation (MV) duration and intensive care unit (ICU) length of stay.Results: In all patients that received continuous field flooding CO2, correction of ventilation for hypercapnia during cardiopulmonary bypass (CPB) was applied with an increase of mean sweep gas air (2.5 L) and monitoring of VCO2 changes. One patient vs. 9 patients of control group reported agitation at discontinuation of anesthesia (p = 0.022). MV duration was 14 ± 3 h vs. 27 ± 4 h (p = 0.016) and ICU length of stay was 33 ± 4 h vs. 42 ± 5 h (p = 0.029). A significant difference was found in the median number of total micro-emboli recorded from release of cross-clamp until 20 min after end of CPB (154 in the continuous CO2 group vs. 261 in the one-shot CO2 control group; p < 0.001). Total micro-emboli from the first 15 min after the release of cross-clamp was 113 in the continuous CO2 group vs. 310 in the control group (p < 0.001). In the continuous CO2 group, the median number of detectable micro-emboli after CPB fell to zero 9 ± 5 min after CPB vs. 19 ± 3 min in the control group (p = 0.85).Conclusion: Continuous field flooding insufflation of CO2 in MIMVR is associated with a lower incidence of micro-emboli and of agitation at discontinuation of anesthesia, along with improved MV duration and ICU length of stay. [ABSTRACT FROM AUTHOR]