In Peru, it was hypothesized that epidemic cholera in 1991 was linked to El Nino, the warm phase of El Nino-Southern Oscillation. While previous studies demonstrated an association in 1997-1998, using cross-sectional data, they did not assess the consistency of this relationship across the decade. Thus, how strong or variable an El Nino-cholera relationship was in Peru or whether El Nino triggered epidemic cholera early in the decade remains unknown. In this study, wavelet and mediation analyses were used to characterize temporal patterns among El Nino, local climate variables (rainfall, river discharge, and air temperature), and cholera incidence in Piura, Peru from 1991 to 2001 and to estimate the mediating effects of local climate on El Nino-cholera relationships. The study hypothesis is that El Nino-related connections with cholera in Piura were transient and interconnected via local climate pathways. Overall, our findings provide evidence that a strong El Nino-cholera link, mediated by local hydrology, existed in the latter part of the 1990s but found no evidence of an El Nino association in the earlier part of the decade, suggesting that El Nino may not have precipitated cholera emergence in Piura. Further examinations of cholera epicenters in Peru are recommended to support these results in Piura. For public health planning, the results may improve existing efforts that utilize El Nino monitoring for preparedness during future climate-related extremes in the region.