Purpose To describe the outcome of adjuvant high fluence photoactivated chromophore for infectious keratitis cross-linking (PACK-CXL) used to treat an advanced form of refractory Acanthamoeba keratitis (AK) diagnosed several months after initial presentation. Observations An otherwise healthy 24-year old female presented with a severe unilateral keratitis. The diagnosis eluded clinicians for several months and when finally confirmed as AK, anti-amoebic therapy was instated and only appeared to be effective after addition of high fluence PACK-CXL. Conclusion and importance In this case of advanced AK, high fluence PACK-CXL treatment given adjuvant to pharmacologic anti-amoebic therapy resulted in lasting pain relief, re-epithelization and eradication of the Acanthamoeba parasite. Given adjuvant to anti-amoebic pharmacotherapy, high fluence PACK-CXL might be a useful method for treating typically refractory advanced AK.