The role of NMDA receptors (NMDARs) in synaptic refinement during development is not well understood. Here, the authors used newborn mice with genetic mosaic deletions of NMDARs at vibrissal relay synapses in the ventral posteromedial thalamus (VPm), which undergo substantial postnatal refinement. At postnatal days 13–14, VPm neurons lacking NMDARs received input from more axons than control VPm neurons. They also had fewer AMPARs, suggesting reduced synapse strength. Thus, both pruning of redundant synapses and strengthening of remaining synapses were disrupted in neurons lacking NMDARs, indicating that NMDARs are required for synapse refinement during development.