The objective of this study was to conduct an incremental cost-effectiveness analysis from the payer's perspective in Singapore of 3 gestational diabetes mellitus screening strategies: universal, targeted, or no screening. A decision tree model assessed the primary outcome: incremental cost per quality-adjusted life year (QALY) gained. Probabilities, costs, and utilities were derived from the literature, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study, and the KK Women's and Children's Hospital's database. Relative to targeted screening using risk factors, universal screening generates an incremental cost-effectiveness ratio (ICER) of $USD10,630/QALY gained. Sensitivity analyses show that disease prevalence rates and intervention effectiveness of glycemic management have the biggest impacts on the ICERs. Based on the model and best available data, universal screening is a cost-effective approach for reducing the complications of gestational diabetes mellitus in Singapore as compared with the targeted screening approach or no screening.