Objective To evaluate the safety and efficacy of topography-guided transepithelial photorefractive keratectomy （T-PRK） in the treatment of high and irregular astigmatism after penetrating keratoplasty （PKP）. Methods In this non-randomized retrospective study， 18 patients （20 eyes） with high or irregular astigmatism after PKP were treated with topography-guided T-PRK. Uncorrected distance visual acuity （UDVA）， corrected distance visual acuity （CDVA）， refraction， corneal topography， and subjective evaluation of visual symptoms were recorded and analyzed both preoperatively and at the last follow-up visit during this study. A Wilcoxon signed-rank test was used for the statistical analysis of UDVA， CDVA， refraction and corneal topography. Results At a mean follow-up time of 12.15±2.06 months postoperatively， mean UDVA and CDVA improved from 1.36±0.42 to 0.65±0.40 （Z=-3.727， P＜0.01）， and from 0.34±0.22 to 0.17±0.14 （Z=-3.607，P＜0.01）， respectively， with 10 eyes gaining two or more lines of CDVA. Moreover， mean sphere decreased from 1.48±3.14 D to -0.19±2.11 D （Z=-2.373， P＜0.05）； mean cylinder was reduced from -7.81±3.43 D to -3.06±1.99 D （Z=-3.792， P＜0.01）； the mean postoperative spherical equivalent （SE） refraction adjusted by intended SE was -1.72±2.55 D. Of all eyes， 3 eyes were within ±0.50 D of the intended refraction， 9 eyes were within ±1.00 D of the intended refraction. The mean corneal irregularity index （IRI） and orthogonal curvature asymmetry decreased from 66.33±22.03 μm to 59.11±14.66 μm （Z=-0.831， P＞0.05）， and from 8.96±4.36 D to 7.44±3.56 D （Z=-2.576， P＜0.05） respectively. All patients reported visual symptoms had improved or remained unchanged. Conclusion Topography-guided T-PRK appears to be a safe and effective treatment for post-PKP high and irregular astigmatism.