Objective: We applied direct cortical stimulation (DCS) to the orbitofrontal cortex (OFC) in neurosurgical patients implanted with intracranial electrodes to probe, with high anatomic precision, the causal link between the OFC and human subjective experience. Methods: We administered 272 instances of DCS at 172 OFC sites in 22 patients with intractable focal epilepsy (from 2011 to 2017), none of whom had seizures originating from the OFC. Results: Our observations revealed a rich variety of affective, olfactory, gustatory, and somatosensory changes in the subjective domain. Elicited experiences were largely neutral or negatively valenced (e.g., aversive smells and tastes, sadness, and anger). Evidence was found for preferential left lateralization of negatively valenced experiences and strong right lateralization of neutral effects. Moreover, most of the elicited effects were observed after stimulation of OFC tissue around the transverse orbital sulcus, and none were seen in the most anterior aspects of the OFC. Conclusions: Our study yielded 3 central findings: first, a dissociation between the “silent” anterior and nonsilent middle/posterior OFC where stimulation clearly elicits changes in subjective experience; second, evidence that the OFC might play a causal role in integrating affect and multimodal sensory experiences; and third, clear evidence for left lateralization of negatively valenced effects. Our findings provide important information for clinicians treating OFC injury or planning OFC resection and scientists seeking to understand the brain basis for the integration of sensation, cognition, and affect.