Background: Opaque bubble layers (OBLs) are a common intraoperative complication during flap creation in femtosecond laser-assisted LASIK (FS-LASIK). This study aims to evaluate how cone and flap sizes can be optimized to minimize OBL risk in VISUMAX 800 FS-LASIK. Methods: This was a retrospective chart review of patients who underwent LASIK with the VISUMAX 800. Eyes were grouped by cone size and laser settings into S cone/M settings and M cone/L settings, in addition to OBL status (OBL vs. non-OBL). Generalized estimating equations were used to account for inter-eye correlation. Flap–cone edge gap was quantified from intraoperative images using FIJI (version 2.17.0, ImageJ). Results: OBL developed in 17 of 226 eyes (7.5%). The majority of OBLs (15/17) occurred in the M cone with L setting group. Eyes that developed OBLs had larger WTWs (p < 0.001) and larger mean flap diameters (p < 0.001). Among eyes with M cones and L settings, image analysis revealed that the average gap between flap and cone edge was significantly larger in the OBL group (p = 0.007). Conclusions: Our findings support the use of VISUMAX 800 in FS-LASIK and suggest that OBL formation may be associated with the distance between flap and cone edges, with larger average flap–cone gaps observed in eyes that developed OBL.