Periprocedural bleeding is associated with an increased risk of mortality during percutaneous coronary intervention (PCI), especially in patients with severe chronic renal insufficiency. Therefore, trans-radial intervention (TRI) should be considered in these patients; however, PCI operators usually avoid this approach because of the risk of radial artery occlusion. We aimed to investigate the associations of TRI and in-hospital complications in these patients. This study included 306 consecutive patients with severe chronic renal insufficiency and/or on dialysis who underwent PCI. Patients were prospectively enrolled and divided according to the access site into TRI group and trans-femoral intervention group. Severe renal insufficiency was defined as estimated glomerular filtration rate < 30 mL/min/1.73 m². Radial access was limited to the opposite side of the arteriovenous fistula in patients on hemodialysis. The primary study endpoint was the composite of in-hospital bleeding complications and death. TRI benefit was evaluated by inverse probability treatment weighted analysis. TRI was performed in 112 (37.3%) patients. TRI group included older patients with significantly lower rates of diabetes mellitus, dialysis, and three-vessel disease. Crossover to the other approach occurred only in TRI group (2.6%). The primary endpoint was significantly lower in TRI group (11.5% vs. 2.6%, P = 0.006). After an inverse probability treatment weighted analysis, TRI was an independent prognostic factor for a decrease in the primary endpoint (OR 0.19; 95% CI 0.051–0.73; P = 0.015). Radial artery occlusion occurred in three patients on dialysis (9.1%). TRI may determine better in-hospital outcomes in patients with severe chronic renal insufficiency and/or on dialysis.