BACKGROUND: Current guidelines recommend lifelong oral anticoagulation (OAC) for patients with atrial fibrillation (AF) based on stroke risk, regardless of AF burden. Post-AF ablation trials report lower-than-expected stroke rates, raising the question of whether OAC could be reserved for periods of AF recurrence: a rhythm-guided pill-in-the-pocket strategy. OBJECTIVE: This study aimed to characterize long-term AF burden post-ablation and modeled rhythm-guided OAC. METHODS: Posthoc analysis of the COMPARE-CRYO trial of patients with paroxysmal AF undergoing first-time cryoablation with continuous implantable cardiac monitor monitoring was conducted. AF episodes were independently adjudicated. Rhythm-guided OAC strategies were modeled in patients with a CHA2DS2-VA score ≥1, triggered by a daily burden ≥6 minutes, ≥1 hour, ≥5.5 hours, and ≥23.5 hours with different OAC window durations. RESULTS: Among 201 patients over a median follow-up of 3.3 years, median daily AF burden was 0% (interquartile range = 0%-0.01%), with AF absent on 96.5% of days. Of 108 patients with recurrence, 40% maintained very low burden (<0.1%), and 36% had low burden (0.1%-1%). Among 139 patients with CHA2DS2-VA ≥1, a restart-and-continue strategy triggered by AF ≥6 minutes resulted in OAC during 32% of follow-up. Pill-in-the-pocket strategies with fixed OAC windows (14 or 30 days) reduced OAC by 90.8%-99.4%. The ≥1-hour threshold with 30-day OAC window provided the most favorable balance, covering 97.5% of time in AF while reducing OAC exposure by 90.8%. CONCLUSIONS: Most patients maintained a consistently low AF burden after cryoablation. Rhythm-guided anticoagulation could substantially reduce OAC, with the ≥1-hour threshold best balancing OAC reduction and time-in-AF coverage. These strategies require prospective evaluation of clinical outcomes.