Abstract. BACKGROUND: A recent multinational clinical trial in preterm infants has demonstrated pulmonary and neurodevelopmental benefits from caffeine therapy. Indications for caffeine use in that study were predominantly for treatment of apnea and facilitation of extubation rather than prophylaxis. There are no recent studies that describe current practice of neonatologists and regional differences in regards to indications for starting, monitoring and discontinuing methylxanthine therapy in premature infants. OBJECTIVE: To characterize the spectrum of current practice and demonstrate the extent to which methylxanthine therapy varies by location. METHODS: A cross-sectional survey of all neonatologists in Thailand, Lebanon, Australia, and a representative sample in the USA regarding management of apnea of prematurity. RESULTS: The response rate was 50% (342/681). The methylxanthine of choice varied greatly across study locations. Prophylactic methylxanthine use is common (62%) among neonatologists in all four study locations. Significant variation exists in almost all aspects of apnea pharmacotherapy practice among neonatologists in different international locations. CONCLUSIONS: Prophylactic use of methylxanthine therapy for apnea of prematurity is widespread. We speculate that this expanded use is possibly attributed to the beneficial effects of caffeine therapy in the Caffeine for Apnea of Prematurity (CAP) Trial.