HYPOTHESIS: Animals with cochlear implantation-induced hearing loss will have a lower endocochlear potential (EP) and decreased strial vascular density. BACKGROUND: The cause of residual hearing loss following cochlear implantation remains poorly understood. Recent work from our lab has shown a correlation between vascular changes in the cochlear lateral wall and postimplantation hearing loss, suggesting a role of the stria vascularis and EP. METHODS: Fourteen young, normal-hearing male albino guinea pigs underwent cochlear implantation using either a cochleostomy (CI-c, n = 9) or an extended round window (CI-eRW, n = 5) approach. Hearing sensitivity was assessed pre- and postoperatively using auditory brainstem response thresholds. Three weeks after implantation, EP measurements were obtained from the first and second turns. Hair cell counts and stria vascularis capillary density measurements were also obtained. RESULTS: The implanted group experienced significant threshold elevations at 8 to 24 kHz (mean threshold shift 9.1 ± 1.1 dB), with a more robust threshold shift observed in the CI-eRW group compared to the CI-c group. Implanted animals had a significantly lower first turn EP (81.4 ± 5.1 mV) compared with controls (87.9 ± 6.1 mV). No differences were observed in the second turn (75.8 ± 12.0 mV for implanted animals compared to 76.5 ± 7.0 mV for controls). There were no significant correlations between turn-specific threshold shifts, EP measurements, or strial blood vessel density. CONCLUSIONS: Reliable EP measurements can be obtained in chronically implanted guinea pigs. Hearing loss after implantation is not explained by changes in strial vascular density or reductions in EP.