Extreme heat (EH) is a growing concern with climate change, and protecting human health requires knowledge of vulnerability factors. We evaluated whether associations between EH (maximum temperature > 97th percentile) and hospitalization for renal, heat and respiratory diseases among people > 65 years differed by individual and area-level characteristics. We used Medicare billing records, airport weather data, U.S. Census data and satellite land cover imagery in 109 US cities, May-September, 1992-2006, in a time-stratified case-crossover design. Interaction terms between EH and individual (> 78 years, black race, sex) and home ZIP-code (percentages of non-green space, high school education, housing built before 1940) characteristics were incorporated in a single model. Next, we pooled city-specific effect estimates or regressed them on quartiles of air conditioning prevalence (ACP) in a multivariate random effects meta-analysis. EH and combined renal/heat/respiratory hospitalization associations were stronger among blacks, the very old, in ZIP codes with lower educational attainment or older housing and in cities with lower ACP. For example, for EH versus non-heat days, we found a 15% (95% CI 11%-19%) increase in renal/heat/respiratory hospitalizations among individuals in ZIP codes with higher percent of older homes in contrast to a 9% (95% CI 6%-12%) increase in hospitalizations in ZIP codes with lower percent older homes. Vulnerability to EH-associated hospitalization may be influenced by age, educational attainment, housing age and ACP.