Jun Zhang, Li Zheng, Chenyao Zheng, Peihong Sun Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Email zhangjun@mskyk.onaliyun.comPurpose: This study was designed to compare the clinical outcomes of three cylindrical treatment strategies using manifest, topographic, and Zhang & Zheng vector-compensated refraction (ZZ VR) cylinders, for topography-guided laser-assisted in situ keratomileusis (LASIK) and to identify the laser programming strategy that optimizes refractive astigmatism outcomes and visual acuity.Methods: Consecutive patients referred for therapeutic refractive surgery between March and September 2018 at a single center were prospectively analyzed. Using double-masked simple randomization, patients were randomly assigned to undergo treatment based on manifest cylinder, topographic cylinder, and ZZ VR cylinder strategies. Uncorrected distance visual acuity and astigmatic refraction were analyzed preoperatively and 6 months postoperatively.Results: A total of 138 eyes from 71 patients met the inclusion criteria. The manifest group consisted of 46 eyes in 24 patients, the topographic group consisted of 43 eyes in 22 patients, and the ZZ VR group consisted of 49 eyes in 25 patients. The absolute residual cylindrical refractions at 6 months postoperatively in these three groups were 0.69 ± 0.32 D, 0.58 ± 0.31 D, and 0.42 ± 0.19 D, respectively (P < 0.001; adjusted P < 0.01 for manifest vs ZZ VR, adjusted P = 0.08 for topographic vs ZZ VR). The percentages of postoperative absolute residual cylindrical power within 0.50 D in the manifest, topographic, and ZZ VR groups were 30.4%, 55.8%, and 59.2%, respectively (P = 0.01; adjusted P = 0.06 for manifest vs topographic, adjusted P = 0.02 for manifest vs ZZ VR).Conclusion: The ZZ VR strategy may achieve better outcomes, as determined by cylindrical correction and visual activity, during topography-guided LASIK.Clinical Trial Registration Number: ChiCTR1900025779.Keywords: astigmatism, corneal wavefront aberration, keratomileusis, laser in situ, refraction