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Background Atrial fibrillation (AF) is a generally acknowledged turning-point of the natural history of hypertrophic cardiomyopathy (HCM);however,data from the cryoballoon ablation (CBA) for AF in HCM patients are relatively scarce.The study aimed to evaluate the efficacy and safety of CBA in HCM patients with AF.Methods We retrospectively analyzed HCM patients among 1253 patients with symptomatic AF who underwent CBA for pulmonary vein isolation in a single center.The study analyzed the AF recurrence and assessed the CBA indexes,including nadir temperature,time-to-isolation,CBA failure,pulmonary vein potentials (PVPs),and redo procedure.Results A total of 108 patients were included (mean age: 59.0 ± 6.9 years),27 patients (25％) had HCM,with the median follow-up duration of 25.5 months.The one-year AF-free rates were 79.0％ vs.63.0％ (non-HCM vs.HCM),while the two-year AF-free rates were 77.8％ vs.55.1％[hazard ratio (HR) =2.758,log-rank P =0.024].Patients with persistent AF had poor AF-free rates compared to those with paroxysmal AF (P ＜ 0.001).The CBA failure was the most common in the right inferior pulmonary veins,which had the lowest PVPs.Multivariate Cox regression analysis indicated that HCM and persistent AF were risk factors for AF recurrence (HR =2.74,95％ CI: 1.29-5.79,P =0.008;and HR =3.97,95％ CI: 1.85-8.54,P ＜ 0.001,respectively).Conclusions The CBA can be effectively and safely used to treat HCM patients with symptomatic AF.The freedom from AF for HCM patients after CBA is relatively low compared to that for non-HCM patients.