The aim of this study was to evaluate a new electrospun P(LLA-CL) nanoscale fibrinogen mesh performance in real-world clinical practice. A prospective, single-center evaluation of Lichtenstein inguinal hernia repair using electrospun P(LLA-CL) nanoscale fibrinogen mesh in elderly patients with comorbid diseases was conducted between 2020 and 2022. A suture reinforcement of transversalis fascia was applied before mesh implantation. Hernia recurrence, pain score and overall complication rate were measured. A total of 52 inguinal hernias in 48 patients were included. The age of patients ranged from 33 to 95 years, with a median of 78 years. Comorbid conditions included cardiopulmonary disease, organ dysfunction, anticoagulant use, diabetes and smoking. By optimizing the physical condition perioperatively, all patients finished treatment successfully. Four cases recurred secondary to direct hernias or combined hernias and were diagnosed in the first 24 case cohort during follow-up. With surgical procedural modification involving strengthening the posterior inguinal floor by reef-up suturing of the transversalis fascia and the inferior edge of mesh slit to accommodate the spermatic cord, no further recurrence was diagnosed. Postoperative pain was mild and the pain score decreased three months after surgery compared to 1 week after surgery (p = 0.0099). No severe complications occurred, while seroma occurred in six cases. Electrospun P(LLA-CL) nanoscale fibrinogen mesh is safe and effective in repairing inguinal hernias in elderly patients with comorbid disease. A strengthening of the transversalis fascia by suturing may enhance the performance of this mesh.© 2023. The Author(s).