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IMPORTANCE: The unprecedented increase in multiple births during the past 3 decades is a major public health concern and parallels the uptake of medically assisted conception. The economic implications of such births are not well understood. OBJECTIVES: To conduct a comprehensive economic and health services assessment of the frequency, duration, and cost of hospital admissions during the first 5 years of life for singleton, twin, and higher-order multiple (HOM) children and to examine the contribution of assisted reproductive technology (ART) to the incidence and cost of multiple births. DESIGN, SETTING, AND PARTICIPANTS: A retrospective population cohort study using individually linked birth, hospital, and death records among 233 850 infants born in Western Australia between October 1993 and September 2003, and followed up to September 2008. EXPOSURES: Multiple-gestation delivery and ART conception. MAIN OUTCOMES AND MEASURES: Odds of stillbirth, prematurity and low birth weight, frequency and length of hospital admissions, the mean costs by plurality, and the independent effect of prematurity on childhood costs. RESULTS: Of 226 624 singleton, 6941 twin, and 285 HOM infants, 1.0% of singletons, 15.4% of twins, and 34.7% of HOM children were conceived following ART. Compared with singletons, twins and HOMs were 3.4 and 9.6 times, respectively, more likely to be stillborn and were 6.4 and 36.7 times, respectively, more likely to die during the neonatal period. Twins and HOMs were 18.7 and 525.1 times, respectively, more likely to be preterm, and 3.6 and 2.8 times, respectively, more likely to be small for gestational age. The mean hospital costs of a singleton, twin, and HOM child to age 5 years were $2730, $8993, and $24 411 (in 2009-2010 US dollars), respectively, with cost differences concentrated in the neonatal period and during the first year of life. Almost 15% of inpatient costs for multiple births could have been avoided if ART twins and HOMs had been born as singletons. CONCLUSIONS AND RELEVANCE: Compared with singletons, multiple-birth infants consume significantly more hospital resources, particularly during the neonatal period and first year of life. A significant proportion of the clinical and economic burden associated with multiple births can be prevented through single-embryo transfer. Increasing ART use worldwide and persistently high ART multiple-birth rates in several countries highlight the need for strategies that encourage single-embryo transfer. The costs from this study can be generalized to other settings.