Although it is well established that the hippocampus is critical for episodic memory, little is known about how the hippocampus interacts with cortical regions during successful memory formation. Here, we used event-related functional magnetic resonance imaging (fMRI) to identify areas that exhibited differential functional connectivity with the hippocampus during processing of novel objects that were subsequently remembered or forgotten on a postscan test. Functional connectivity with the hippocampus was enhanced during successful, as compared with unsuccessful, memory formation, in a distributed network of limbic cortical areas—including perirhinal, orbitofrontal, and retrosplenial/posterior cingulate cortex—that are anatomically connected with the hippocampal formation. Increased connectivity was also observed in lateral temporal, medial parietal, and medial occipital cortex. These findings demonstrate that successful memory formation is associated with transient increases in cortico-hippocampal interaction.