SummaryBackground and objectives This study examined the associations between homelessness and clinical outcomes of CKD among adults from the urban healthcare safety net.Design, setting, participants, & measurements This retrospective cohort study examined 15,343 adults with CKD stages 3-5 who received ambulatory care during 1996-2005 from the Community Health Network of San Francisco. Main outcome measures were time to ESRD or death and frequency of emergency department visits and hospitalizations.Results Overall, 858 persons (6%) with CKD stages 3-5 were homeless. Homeless adults were younger, were disproportionately male and uninsured, and suffered from far higher rates of depression and substance abuse compared with adults with stable housing (P,0.001 for all comparisons). Over a median follow-up of 2.8 years (interquartile range=1.4-6.1), homeless adults experienced significantly higher crude risk of ESRD or death (hazard ratio=1.82, 95% confidence interval=1.49-2.22) compared with housed adults. This elevated risk was attenuated but remained significantly higher (adjusted hazard ratio=1.28, 95% confidence interval=1.04-1.58) after controlling for differences in sociodemographics, comorbid conditions, and laboratory variables. Homeless adults were also far more likely to use acute care services (median [interquartile range] number of emergency department visits was 9 [4-20] versus 1 [0-4], P,0.001) than housed counterparts.Conclusions Homeless adults with CKD suffer from increased morbidity and mortality and use costly acute care services far more frequently than peers who are stably housed. These findings warrant additional inquiry into the unmet health needs of the homeless with CKD to provide appropriate and effective care to this disadvantaged group.