BACKGROUND: Pulsed field ablation (PFA) of atrial fibrillation has been rapidly adopted, partly because of safety expectations compared with thermal ablation. Comparative safety data between the 2 modalities remain limited. METHODS: We conducted a prospective registry analyzing consecutive atrial fibrillation ablations at a high-volume US academic center between 2022 and 2026. The primary end point was stroke or transient ischemic attack (TIA) within 30 days, independently adjudicated by blinded neurologists. Secondary end points included death and other procedural complications. Propensity score methods with inverse probability of treatment weighting were used to balance differences in patient characteristics. Differences in the procedural workflow of PFA versus radiofrequency ablation (RFA) were evaluated with exploratory mediation analyses. RESULTS: A total of 4221 ablation procedures (2077 RFA and 2144 PFA: 68.7% Farawave, 23.3% Sphere 9, 6.9% Varipulse, 0.7% PulseSelect) was performed by 12 operators. Patients receiving PFA and RFA had similar baseline characteristics (mean age, 67 years; 31% female; 47% persistent atrial fibrillation; 7% previous stroke/TIA), which were balanced after inverse probability of treatment weighting. Compared with RFA, PFA procedures were shorter (108 versus 144 minutes) and included more frequent posterior wall isolation (57% versus 31%). The 30-day rate of stroke/TIA was significantly higher for PFA cases (10 events; 0.47%) compared with RFA (2 events; 0.10%) in both unweighted and propensity score-weighted analyses (weighted risk difference, 0.36% [95% CI, 0.03%-0.70%]; P=0.03). Stroke/TIA events were evenly distributed throughout the study period with no clustering around the time of PFA adoption or operators (with no operator associated with ≥2 events). Exploratory mediation models were limited by the low event rates and did not identify more extensive ablation as an independent risk factor for stroke. Weighted rates of other procedural complications were low (<1%) and similar between PFA and RFA groups. CONCLUSIONS: In a high-volume, single-center registry with high clinical granularity and systematic patient follow-up, PFA was associated with a significantly higher risk of stroke/TIA at 30 days compared with RFA. These results call for enhanced postmarket surveillance and dedicated prospective evaluation as the PFA procedural volume continues to exponentially increase.