BACKGROUND: The number of catheter ablations performed for atrial fibrillation (AF) has increased dramatically over the past several years. Regional variation in left atrial (LA) wall thickness is known to exist but have not been described in detail. AF ablation success and complication rates may be related to regional differences in LA wall thickness. OBJECTIVE: To evaluate differences in transmural wall thickness in five pre-defined anatomic areas within the LA which are commonly targeted for AF ablation. MATERIALS AND METHODS: We measured LA wall transmural thickness in 34 human heart specimens using calipers in five anatomic areas frequently targeted during AF ablation (anterior wall, septum, mitral isthmus, posterior wall and roof). RESULTS: The autopsied individuals were 53% female, 67.7% had CAD, 14.7% had atrial fibrillation, 61.8% had hypertension, and 21.6% had congestive heart failure. The roof was the thinnest region with mean thickness measuring significantly less than each other area (p 0.005 for the posterior wall and <0.001 for all other areas). The septum was the thickest region with mean thickness measuring significantly greater than each other area (p = 0.05, 0.001, <0.001, <0.001 measured against the anterior wall, isthmus, posterior wall and roof, respectively). CONCLUSIONS: Significant regional differences exist for mean left atrial wall thickness among the different anatomic areas within the left atrium which are often targeted during catheter ablation of AF. These differences may have significant implications in determining the ideal intensity and total duration of radiofrequency energy required to achieve a safe and successful ablation.