Retinopathy of prematurity (ROP) examinations in the NICU are necessary to protect vision in premature infants, but the examinations are associated with risk and discomfort. ROP examination risks include adverse effects from mydriatic agents, systemic responses to the stress of examination, and nosocomial infection. Infant discomfort may be lessened by limiting examination length and possibly by measures such as topical anesthetic, oral sucrose, and certain nonpharmacologic techniques. A well-organized ROP service facilitates appropriate scheduling of examinations and education of the infant's parents. This article addresses causes of risk and infant discomfort, providing a framework for developing a safe and efficient ROP service while minimizing infant discomfort.