Background: Paroxysmal atrial fibrillation (AF) is closely related to pathophysiologic processes and clinical outcomes. However, it is uncertain whether cryoablation of pulmonary veins isolation is effective and safe for patients of symptomatic and drug-refractory AF type within 24-hour episode duration. Methods: The patients were designed into Group A (253 patients of paroxysmal AF within 24-hour episode duration) and Group B (253 patients of paroxysmal AF lasted for 24 hours or longer) on a 1:1 basis by identical propensity scores. Mortality, stroke/transient ischemic attack (TIA) and complications relevant to the cryoablation procedure were compared and recurrence of atrial tachyarrhythmia was analyzed for clinical independent predictors. Results: The rate of atrial tachyarrhythmia recurrence was 21.74% in Group A and 30.04% in Group B, respectively (P=0.042). At 12-month follow-up from procedure, lower incidences of stroke/TIA endpoint of the patients were observed in Group A compared with Group B by Kaplan–Meier analysis [HR 0.34 (0.13–0.87), P= 0.025]. No significant differences about mortality and complications relevant to the cryoablation procedure were observed between Group A and Group B. Moreover, adjusted multivariable Cox regression analysis showed that < 24-hour paroxysmal AF type (HR 0.644, 95% CI: 0.455–0.913, P=0.014) and left atrium diameter (>40 mm) (HR 1.696, 95% CI: 1.046–2.750, P=0.032) were independently associated with the incidence of recurrence of atrial tachyarrhythmia in the study. Conclusions: Cryoablation of AF within 24-hour episode duration is effective and safe for patients with paroxysmal AF.