Previous studies have demonstrated safety and efficacy using 6.0 and 6.5 mm optical zones in the WaveLight EX500 Excimer Laser System but have not evaluated if differing optical zone sizes influence refractive outcomes. This study examines visual outcomes between two study populations undergoing LASIK with either a 6.0 mm (1332 patients) or 6.5 mm (1332 patients) optical zone. Outcomes were further stratified by severity of myopia (low, moderate, and high) and astigmatism (low and high). Patients were matched by age and preoperative manifest sphere and cylinder. Postoperative measurements were then compared. The 6.5 mm group demonstrated better postoperative manifest refractive spherical equivalent (MRSE), manifest sphere, and absolute value of the difference in actual and target spherical equivalent refraction (|∆ SEQ|), within the total population, moderate myopia, and low astigmatism groups, but this did not lead to improved postoperative uncorrected distance visual acuity (UDVA) or best corrected distance visual acuity (CDVA). Though astigmatic correction and postoperative angle of error were similar between optical zone sizes, they were significantly worse with high myopia. Overall, this study demonstrates differences in visual outcomes between the 6.0 and 6.5 mm optical zone sizes that may warrant consideration; however, essentially, the results are comparable between them.