Background: Anatomic variations of the patent foramen ovale (PFO) are commonly observed, yet limited research has investigated their impact on clinical outcomes following transcatheter closure. We aimed to explore the association between PFO morphology and clinical outcomes. Methods: Consecutive patients with cryptogenic stroke who underwent PFO closure were prospectively enrolled at a single center from September 2019 to April 2023. Patients were categorized into simple and complex groups based on PFO morphology. Composite events were compared between the two groups during a median follow-up of 24 months, including all-cause mortality, recurrent stroke, residual moderate or severe shunt, and symptomatic atrial fibrillation. Results: A total of 247 patients were enrolled, with a mean age of 41.9 +/- 13.0 years and 45.3% males. Ninety-one (36.8%) patients had complex PFO. These individuals were older (45.4 +/- 12.5 years vs. 39.9 +/- 12.9 years; P = 0.001), more males (56.0% vs. 39.1%; P = 0.010), had longer procedure times (54 +/- 32 min vs 46 +/- 29 min; P = 0.044), and had a higher rate of using delivery sheath-assisted crossing of the PFO (22.0% vs 12.8%; P = 0.040) than those with simple PFO. The estimated event rates were 27.9% and 11.3% (P = 0.006) in the complex and simple PFO groups, respectively (12.9 events and 5.2 events per 100 person-years; P = 0.001). After adjusting for age, sex, hypertension, diabetes, smoking, device type, and left atrial diameters, complex PFO remained independently associated with composite events (HR 2.10, 95%CI 1.06-4.17, P = 0.034). Conclusions: Patients with complex PFO may suffer from a higher risk of adverse events following transcatheter PFO closure.