To report mid-term outcomes of renal-mesenteric target arteries (TA) after fenestrated-branched endovascular aortic repair (FB-EVAR) of complex abdominal (CAAAs) and thoracoabdominal aortic aneurysm (TAAAs). TA instability (TAI) is the most frequent indication for reintervention after FB-EVAR. Data from consecutive patients enrolled in nine prospective non-randomized physician-sponsored investigational device exemption (PS-IDE) studies between 2005 and 2020 were reviewed. TA outcomes through 5 years of follow-up were analyzed for vessels incorporated by fenestrations or directional branches (DBs), including TA patency, endoleak, integrity failure, reintervention, and instability. A total of 1,681 patients had 6349 renal-mesenteric arteries were targeted using 3720 fenestrations (59%), 2435 DBs (38%) and 194 scallops (3%). Mean follow was 23±21 months. At 5-years, TAs incorporated by fenestrations had higher primary (95±1% vs. 91±1%, P<0.001 ) and secondary patency (98±1% vs. 94±1%, P<0.001) , and higher freedom from TAI (87±2% vs. 84±2%, P=0.002) compared to TAs incorporated by DBs, with no differences in other TA events. DBs targeted by balloon-expandable stent-grafts (BESGs) had significantly lower freedom from TAI (78±4% vs. 88±1%, P=0.006 ), TA endoleak (87±3% vs. 97±1%, P<0.001 ), and TA reintervention (83±4% vs. 95±1%, P<0.00 1 ) compared to those targeted by self-expandable stent-grafts (SESGs). Incorporation of renal and mesenteric TA during FB-EVAR is safe and durable with high 5-year patency rates and low freedom from TAI. DBs have lower patency rates and lower freedom from TAI than fenestrations, with better performance for SESGs as compared to BESGs.