Background: Pulsed field ablation (PFA) and radiofrequency ablation (RFA) exhibit distinct mechanisms of tissue injury, leading to differential impacts on perioperative inflammatory marker expression and myocardial injury in patients undergoing atrial fibrillation ablation. Objective: To compare inflammatory and myocardial injury responses between patients undergoing pulmonary vein isolation (PVI) with pulsed field ablation (PFA) versus radiofrequency ablation (RFA). Methods: Consecutive patients with paroxysmal atrial fibrillation were prospectively enrolled and randomized to undergo pulsed field ablation (PFA) or radiofrequency ablation (RFA) for pulmonary vein isolation (PVI). Plasma inflammatory markers (interleukin-1β, interleukin-4, interleukin-6, interleukin-10, C-reactive protein [CRP], tumor necrosis factor-alpha [TNF], procalcitonin [PCT]) and myocardial injury biomarkers (cardiac troponin T [cTnT], creatine kinase-MB [CK-MB]) were measured at preoperative baseline and 24 hours post-procedure. Results: A total of 179 patients were enrolled (PFA group: 66; RFA group: 113). Baseline characteristics were comparable between groups (age: 61 vs 65 years; renal function, hypertension, diabetes mellitus, etc.). At 24 hours post-procedure, PFA was associated with significantly greater myocardial injury biomarker release (troponin T: 1.3 vs 0.75 ng/mL, P<0.001; CK-MB: 19.7 vs 6.0 ng/mL, P<0.001). Inflammatory responses showed divergent patterns: CRP increased post-PFA but without statistical significance, whereas IL-6 (24.68 vs 6.53 pg/mL, P<0.001) and TNF-α demonstrated marked elevations in the RFA group. Conclusion: Patients undergoing pulsed field ablation (PFA) exhibited significantly greater postprocedural myocardial injury compared to patients treated with radiofrequency ablation (RFA), yet demonstrated attenuated inflammatory responses following pulmonary vein isolation (PVI).