In vivo studies suggest that precise firing of neurons is important for correct sensory representation. Principal neocortical neurons fire imprecisely when repeatedly activated by fixed sensory stimuli or current depolarizations. Here we show that in contrast to pyramidal neurons, firing in neocortical GABAergic fast-spiking (FS) interneurons is quite precise. FS interneurons are self-innervated by powerful GABAergic autaptic connections reliably activated after each spike, suggesting that autapses strongly regulate FS-cell spike timing. Indeed, blockade of autaptic transmission degraded temporal precision in multiple ways. Under these conditions, realistic dynamic-clamp hyperpolarizing autapses restored precision of spike timing, even in the presence of synaptic noise. Furthermore, firing precision was increased in pyramidal neurons by artificial GABAergic autaptic conductances, suggesting that tightly coupled synaptic feedback inhibition regulates spike timing in principal cells. Thus, well-timed inhibition, whether autaptic or synaptic, facilitates precise spike timing and promotes synchronized cortical network oscillations relevant to several behaviors.