Inguinal hernia repair is performed over 20 million times annually, with outcomes reflecting mechanical reconstruction and immune activation. This study compared autoplasty and tension-free alloplasty for primary inguinal hernias, focusing on clinical outcomes and inflammatory responses. This prospective single-center study compared tissue-based autoplasty (Shouldice/Spasokukotsky) with tension-free mesh alloplasty (Lichtenstein) in 118 adults (mean age 46 ± 12.1 years; 93% male; autoplasty, n = 50; alloplasty, n = 68). Pain (verbal descriptor scale), complications, hospital stay, and systemic markers (C-reactive protein, neutrophil-to-lymphocyte ratio, interleukin-6, tumor necrosis factor-alpha, lymphocyte count) were assessed (p < 0.05). Alloplasty showed faster operation (48.4 ± 1.5 vs. 59.6 ± 2.6 min), less pain (day 1: 4.5 ± 0.5 vs. 5.7 ± 0.6; day 2: 1.1 ± 0.2 vs. 2.4 ± 0.3; day 5: 0.5 ± 0.1 vs. 1.2 ± 0.2), earlier walking (7.2 ± 2.1 vs. 21.4 ± 3.6 h), fewer complications (8.4% vs. 28.8%), and reduced hospitalization (3.6 ± 0.9 vs. 5.1 ± 1.2 days; all p < 0.05). Autoplasty showed higher inflammatory markers (C-reactive protein 32.5 ± 6.8 vs. 21.3 ± 5.4 mg/L; neutrophil-to-lymphocyte ratio 5.8 ± 1.2 vs. 3.9 ± 0.9; interleukin-6 48.7 ± 10.2 vs. 29.4 ± 8.6 pg/mL; tumor necrosis factor-alpha 26.5 ± 7.3 vs. 17.2 ± 5.8 pg/mL; all significant). Operative time was correlated with pain (r = 0.64; p < 0.01) and complications (r = 0.48; p < 0.05). Tension-free alloplasty improved recovery and reduced immune activation; however, non-randomization, single-center design, and limited follow-up constrain long-term inferences of the study.