Cross-linking of corneal collagen (CXL) is a promising approach for the treatment of keratoconus and secondary ectasia. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subjected to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze, permanent scars, endothelial damage, treatment failure, sterile infiltrates, and herpes reactivation are the other reported complications of this procedure. Cross-linking is a low-invasive procedure with low complication and failure rate but it may have direct or primary complications due to incorrect technique application or incorrect patient's inclusion and indirect or secondary complications related to therapeutic soft contact lens, patient’s poor hygiene, and undiagnosed concomitant ocular surface diseases.