To report the outcome of stepwise ablation using topography-guided photorefractive keratectomy to treat irregular astigmatism after either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK). This is a retrospective, interventional analysis including patients with irregular astigmatism after either PKP or DALK, who underwent topography-guided photorefractive keratectomy. The entire cohort was analyzed, as well as the PKP and DALK groups separately. Analysis of factors associated with a better outcome was also performed. Thirty-four eyes of 34 patients (20 PKP patients and 14 DALK patients) aged 47.4 ± 15.9 years were included. Twenty-one patients underwent more than 1 ablation. Refractive stability and a minimal period of 5 months were required before repeat ablation. The average follow-up duration was 17.0 ± 6.0 months. Corrected distance visual acuity (CDVA) improved significantly from 0.22 ± 0.14 logarithm of the minimum angle of resolution (logMAR) to 0.14 ± 0.12 logMAR at final follow-up (P = 0.035). Uncorrected distance visual acuity (UDVA) improved significantly from 0.90 ± 0.54 logMAR to 0.57 ± 0.40 logMAR at final follow-up (P = 0.004). CDVA and UDVA improved by ≥1 Snellen lines in 54.2% and 70.8% of the eyes, respectively, and by ≥3 Snellen lines in 16.7% and 54.2% of the eyes, respectively. Statistically significant improvement was seen in optical aberrometry indices (total root mean square, higher-order aberration root mean square, defocus, coma, trefoil, and spherical aberration). The difference between PKP and DALK in either CDVA (P = 0.562) or UDVA (P = 0.384) improvement was nonsignificant. The stepwise topography-guided photorefractive keratectomy approach in cases of irregular astigmatism after PKP or DALK can help improve visual acuity outcomes. Patients should be appropriately counseled that more than 1 treatment will likely be needed.