To better understand the controls on the opportunistic human pathogen Vibrio vulnificus in warm tropical waters, we conducted a year-long investigation in the Ala Wai Canal, a channelized estuary in Honolulu, HI. The abundance of V. vulnificus as determined by qPCR of the hemolysin gene (vvhA), varied spatially and temporally over four orders of magnitude (≤ 3 to 14,000 mL-1). Unlike in temperate and subtropical systems, temperatures were persistently warm (19–31°C) and explained little of the variability in V. vulnificus abundance. Salinity (1–36 ppt) had a significant, but non-linear, relationship with V. vulnificus abundance with highest abundances (> 2,500 mL-1) observed only at salinities from 7 to 22 ppt. V. vulnificus abundances were lower on average in the summer dry season when waters were warmer but more saline. Highest canal-wide average abundances were observed during a time of modest rainfall when moderate salinities and elevated concentrations of reduced nitrogen species and silica suggested a groundwater influence. Distinguishing the abundances of two genotypes of V. vulnificus (C-type and E-type) suggest that C-type strains, which are responsible for most human infections, were usually less abundant (25% on average), but their relative contribution was greater at higher salinities, suggesting a broader salinity tolerance. Generalized regression models suggested up to 67% of sample-to-sample variation in log-transformed V. vulnificus abundance was explained (n = 202) using the measured environmental variables, and up to 97% of the monthly variation in canal-wide average concentrations (n = 13) was explained with the best subset of four variables.