Aims: Catheter ablation (CA) for atrial fibrillation (AF) has a considerable risk of procedural complications. Major vascular complications (MVCs) appear to be the most frequent. This study investigated gender differences in MVCs in patients undergoing CA for AF. Methods: A total of 4734 CAs for AF (65% paroxysmal, 26% repeated procedures) were performed at our center between January 2006 and August 2018. Patients (71% males) aged 60 ± 10 years and had body mass index of 29 ± 4 kg/m2. Radiofrequency point-by-point ablation was employed in 96.3% procedures with the use of 3D navigation systems and facilitated by intracardiac echocardiography. Pulmonary vein isolation was mandatory; cavotricuspid isthmus and left atrial substrate ablation were performed in 22% and 38% procedures, respectively. MVCs were defined as those that resulted in permanent injury, required intervention, or prolonged hospitalization. Their rates and risk factors were compared between genders. Results: A total of 112 (2.4%) MVCs were detected: 54/1512 (3.5%) in females and 58/3222 (1.8%) in males (P < 0.0001). On multivariate analysis, lower body height was the only risk factor for MVCs in females (P = 0.0005). On the contrary, advanced age was associated with MVCs in males (P = 0.006). Conclusion: Females have a higher risk of MVCs following CA for AF compared to males. This difference is driven by lower body size in females. Low body height in females and advanced age in males are independent predictors of MVCs. US-guided venipuncture lowered the MVC rate in males.