Mission Bay, CA is a precious aquatic resource for the San Diego region, offering swimming, boating, sailing and other aquatic recreational opportunities. However, for decades, the City of San Diego has recognized the issue of the microbial contamination of Mission Bay. Indeed, in past decades Mission Bay has had more beach postings and closures as a result of elevated bacterial levels than any other beach in San Diego County. This has resulted in the entire bay being listed as an impaired water body in 1998 under Section 303(d) of the Clean Water Act for exceedances of indicator bacterial standards. In response, the City of San Diego and has taken a number of concrete actions and developed implementable strategies to protect its water quality. Although these efforts were somewhat successful in reducing the number of exceedances of water quality standards in areas of Mission Bay, there has been a lack of a comprehensive evaluation of whether these improvements have continued to improve the water quality. The present study was meant to fill this gap in our understanding of the recent status and trends of the microbial water quality in Mission Bay by performing a statistical trend and spatial analysis of fecal indicator densities throughout Mission Bay. The results of the trend analysis showed that only three out of nine sites in the Bay actually showed significant improvement in microbial water quality over the past two decades. Furthermore, Kruskal-Wallis non-parametric analyses, showed that while there are significant site-specific differences in enterococci densities among the stations studied in Mission Bay, that there is no clear statistical evidence that sites on the east side of Mission Bay are significantly more contaminated than other sites in the northern and middle parts of Mission Bay. Indeed, in Mission Bay where fecal pollution is not only ubiquitous due to avian sources, but also may vary both temporally and spatially, future remediation of microbial contamination will remain a challenge.