Background: Among various treatment modalities of actinic keratosis (AK), ablative fractional laser-assisted photodynamic therapy (fractional PDT) has shown higher efficacy despite shorter incubation time. However, there are lack of real-world studies on the therapeutic response of ablative PDT for AK and the factors that can predict the therapeutic response. Purpose: The aim of this study was to analyze the association between clinical characteristics and treatment outcomes of fractional PDT. Methods: One hundred fifty-six patients who were histologically diagnosed with AK and treated with fractional PDT were retrospectively reviewed. The Kruskal–Wallis test was used to compare treatment session differences according to grades. Results: In multivariate analysis, the grade 2 category tended to be more clinically nonresponders than the grade 1 (OR, 5.17; 95% CI, 1.011–26.439; p =.048) and the group treated four or more times with ablative fractional laser-assisted PDT were more likely to show no response compared with the single treatment session group (OR, 8.78; 95% CI, 1.355–56.874; p =.023). Treatment sessions were significantly lower in grade 1 (1.72 ± 0.63, mean ± SD) when compared to grades 2 and 3, respectively (2.17 ± 0.76; 2.60 ± 1.60, mean ± SD). Recurrence was highest in grade 2, and most of them occurred after 1 year. Conclusion: On average, two treatment sessions are sufficient for AK lesions, but the thicker the lesion, the more treatment sessions may be required. Although there are relatively smaller number of grade 3 patients were included, recurrence was more frequent in higher grade of AK category, which needs special attention to thicker lesions.