Microwave ablation is a minimally invasive treatment modality for malignant and benign tumors in several organs. While many microwave ablation antennas have been described in the literature, most have been designed assuming normal ambient tissue and have not accounted for tissue property changes that occur during intense heating. We analyzed three optimization approaches for canonical monopole and dual‐slot antennas: minimal reflection, spherical specific absorption rate (SAR) pattern, and spherical ablation zone. Simulated ablations with each optimal design were also validated in ex vivo liver tissue. Optimized designs for minimal reflection matched previously published results, while designs optimized for spherical SAR and spherical ablation yielded novel geometries. Surprisingly, optimization for spherical SAR rendered the most spherical ablation zones in ex vivo tissue. Optimizations for minimal reflection and spherical ablation zone did not achieve the most spherical ablation zones in experiments. These results point to the need for greater accuracy in dielectric and thermal tissue models to improve simulation‐aided design, and to the potential for continued refinement in microwave ablation antenna design.