Residential segregation is a major area of research in demography. Most prior investigations have focused on the segregation of racial/ethnic minorities from the majority white group in cities and metropolitan areas of the United States and several other countries. Few analyses have dealt with the spatial segregation of sexual minorities from the majority. In this paper, we analyze the residential segregation of gay male and lesbian households from heterosexual married and heterosexual cohabiting households. We use two dissimilarity measures of residential segregation and draw on data from the American Community Surveys for 2008 through 2012 to compute segregation scores for the 100 metropolitan statistical areas (MSAs) with the largest gay male and lesbian populations around the year 2010. We show that there is a sizable amount of homosexual-heterosexual residential segregation and that it appears to be a different phenomenon from racial and ethnic residential segregation. We also show that gay male households are more segregated from different-sex partnered households than are lesbian households, and that levels of segregation vary positively across the MSAs with the size of the gay male and lesbian populations.