Introduction: The aim of this study was to evaluate the incidence rate of technical failure of graft patency while performing intra-operative angiography after coronary artery bypass grafting. Methods: This prospective pilot study included 50 patients with multi-vessel coronary artery disease who underwent coronary artery bypass grafting, in addition to intra-operative angiographic graft assessments, on open-chest. Overall, 144 grafts and 160 distal anastomoses were assessed in a hybrid operating room. Results: Intra-operative angiography allowed the identification of 23 angiographic defects (15.9% of all grafts) in 22 patients (44%): three graft defects (2% of all grafts), 17 anastomotic defects (10.6% of all distal anastomoses), and three target artery errors (1.8% of all grafted arteries). Ten re-interventions (43.4%) were performed based on the angiographic defects detected. During the follow-up period, computed tomography angiography of the attached grafts at a mean of 224 days (range, 80–318 days) showed that all repaired grafts were patent. During surgery, the total mean dose of radiation was 1.848 ± 0.54 mSv (range, 0.78–3.4 mSv) per patient and investigation time was 19.4 ± 4.94 minute (range, 9–31 minute). Conclusions: Intra-operative angiography is a powerful tool allowing the identification of graft defects, anastomotic defects and target vessel errors. Assuming relatively low level of exposure to radiation and short investigation time, intra-operative angiography could be included in routine practice as safe procedure improving surgery quality.