We sought to evaluate the safety and efficacy of totally percutaneous femoral access (TPFA) for fenestrated-branched endovascular aortic repair (F/B-EVAR) of pararenal-thoracoabdominal aortic aneurysms (PRAs/TAAAs). We reviewed all consecutive patients enrolled in single-center prospective non-randomized single-arm study to investigate F/B-EVAR for PRAs/TAAAs (2013-2017). Percutaneous approach was selected in all patients when anatomically feasible; otherwise, surgical femoral access (SFA), with or without construction of temporary prosthetic conduit, was selected. Primary outcomes were technical success, mortality, major adverse events (MAEs) and major vascular access complications. A total of 231 patients were included in the study: TPFA was possible in 163 (70%) with technical success rate of 93%, while 68 (30%) required SFA. Patients with TPFA and SFA had similar mortality rate of 1%. The rate of MAEs for TPFA was 20% versus 38% for SFA (p = .07). The trend was mainly driven by reduced rates of estimated blood loss (EBL) ≥ 1L (6% vs 21%, p = .001) and acute myocardial infarction (2% vs 9%, p = .03). Similarly, TPFA carried a significantly lower rate of major vascular access complications as compared with SFA (6% vs 21%, p < .001; adjusted OR 3.4, 95% CI 1.3-8.9, p = .01). A percutaneous-first approach for elective F/B-EVAR of PRAs/TAAAs is safe, feasible and effective when proper patient selection is provided. When the presence of hostile iliofemoral anatomy requires open-vessel exposure, higher rates of perioperative major bleeding, cardiac events and access complications may be expected. Level 3 (single-center prospective non-randomized single-arm study).