Purpose To investigate the efficacy of photoactivated chromophore corneal collagen cross-linking (PACK)-CXL in the management of treatment-resistant infectious keratitis. Design Observational cohort study. Participants Forty-two eyes from 41 patients with treatment-resistant infectious keratitis. Methods Eyes underwent PACK-CXL treatment with the Dresden modified protocol in addition to standard antimicrobial therapy. The primary endpoint was the size of the corneal ulcer. Descriptive statistics, Wilcoxon rank test, McNemar test and Spearman correlation coefficient were used for statistical analysis, and p values lower than 0.05 were considered statistically significant. Results Success rate at third postoperative month was of 90.5%. Statistical analyses showed a significant effect of (PACK)‑CXL with standard antimicrobial therapy to reduce corneal ulcer size (p=0.031). Conclusion As adjuvant therapy to standard antimicrobial treatment, PACK-CXL improves the outcomes in patients with treatment-resistant corneal ulcers.