Background— Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR. Methods and Results— Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%]; P =0.001) and number (3.4±4.9 versus 1.2±1.8; P =0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL; P =0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade: r =0.46; P =0.0001) and SAVR (concomitant coronary artery bypass grafting: r =−0.33; P =0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0; P <0.0001) and 6 months (40.4±9.3; P <0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2; P <0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction. Conclusions— Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.