Catheter ablation (CA) is a potentially curative therapy for paroxysmal atrial fibrillation, however up to 50% of patients may require a repeat procedure to achieve the best results. While this may be due to insufficient radiofrequency (RF) energy delivery to achieve transmural, contiguous ablation lesions (TAL), excessive RF application may result in extracardiac injury and complications. We aim to evaluate optimal RFCA temperature settings for variable atrial tissue depth and blood flow conditions. Heat spread in atrial tissue and blood was simulated using the Pennes bioheat equation with an additional convective term in the blood. The minimum catheter contact time required for TAL formation increased with increasing either atrial wall thickness (AWT) or laminar flow velocity (LFV). Thus, during ablation of atrial tissue regions with AWT of 1 and 5.5 mm and LFV of 0.1 m/s, TALs were formed in 12 and 153 s, respectively. When LFV was increased to 1.2 m/s, the TAL formation time increased to 21 and 174 s. The maximum temperature in the blood volume stayed below the coagulation risk threshold of 70°C for all AWT values with LFVs over 0.6 m/s, but raised above the threshold for LFV ≦ 0.6 m/s and AWT > 1.5 mm. This study demonstrates the potential for optimizing RFCA settings according to atrial tissue depth and flow, which may improve the efficacy of RFCA therapy.