To evaluate the outcomes of transepithelial photorefractive keratectomy (PRK) in moderate to high astigmatism with a non-wavefront-guided aberration-neutral ablation profile using SmartPulse allocation.In this retrospective study, myopic patients with a preoperative cylinder of 2.00 diopters (D) or greater were analyzed at 3 months of follow-up. Transepithelial PRK treatments were performed in each patient with the Amaris 1050RS laser (SCHWIND eye-tech-solutions, Kleinostheim, Germany) creating aspheric ablation profiles by applying a SmartPulse allocation. Standard examinations and wavefront analyses were included for low and high ocular residual astigmatism subgroups.Fifty-eight eyes (44 patients) were included in the cohort. The eyes were divided into separate ocular residual astigmatism subgroups: 17 eyes presented with less than 0.50 D (low ocular residual astigmatism) and 24 eyes with greater than 0.75 D (high ocular residual astigmatism). The mean refractive cylinder in the entire cohort was 2.84 ± 0.86 D preoperatively and 0.40 ± 0.39 D postoperatively, with 81% of the eyes within 0.75 D of the target astigmatism. At 3 months of follow-up, significant improvement (P < .05) was seen in terms of sphere, cylinder, spherical equivalent, and uncorrected (UDVA) and corrected (CDVA) distance visual acuity. CDVA improved in 40% of eyes and 3% of eyes lost one line of CDVA. No clinically relevant changes were seen in higher order aberrations. The refractive changes showed an excellent match with the keratometric changes. The difference between the low and high ocular residual astigmatism subgroups was not significant except for the change of Snellen lines of CDVA (P < .05).Transepithelial PRK using a non-wavefront-guided aberration-neutral ablation profile performed by applying SmartPulse allocation yielded excellent visual outcomes. The preoperative astigmatism was reduced to subclinical values. Both subgroups were effective in terms of UDVA, CDVA, spherical and astigmatic correction, and preserving higher order aberrations. However, the low ocular residual astigmatism subgroup was slightly more prone to gain lines of CDVA. [J Refract Surg. 2018;34(7):466-474.].