- Purpose: To evaluate the effect of accelerated corneal cross-linking with photoactivated chromophore (PACK-CXL) as additional treatment for therapy-resistant infectious keratitis. Methods: In this interventional cohort study, 20 patients (11 men and 9 women), aged 65.5 (interquartile range = 21.5–78.5) years, who were hospitalized for moderate-sized therapy-resistant bacterial corneal ulcers (11/20 microbiologically confirmed) were treated with hypoosmolar 0.1% riboflavin solution and Ultraviolet A (UVA) irradiation for 3 minutes at 30 mW/cm2 (5.4 J/cm2) as additional therapy to standard antimicrobial treatment. Results: We did not observe any adverse effects of accelerated PACK-CXL on the corneal stroma or limbus. The median ulcer size was 3.00 (2.63–4.50) mm, the median time to reepithelialization was 6.50 (5.00–18.0) days, and the mean hospitalization period was 8.5 ± 4.5 days. Tectonic keratoplasty became necessary in 1 patient (5%). Conclusions: Our results suggest that accelerated PACK-CXL may provide an antimicrobial effect similar to the 1 low-intensity, slow setting (30 minutes at 3 mW/cm2) and may be used as additional treatment in moderate-sized therapy-resistant infectious keratitis.