Objectives. We examined whether neighborhood social characteristics (income distribution and family fragmentation) and physical characteristics (clean sidewalks and dilapidated housing) were associated with the risk of fatalities caused by analgesic overdose. Methods. In a case-control study, we compared 447 unintentional analgesic opioid overdose fatalities (cases) with 3436 unintentional nonoverdose fatalities and 2530 heroin overdose fatalities (controls) occurring in 59 New York City neighborhoods between 2000 and 2006. Results. Analgesic overdose fatalities were less likely than nonoverdose unintentional fatalities to have occurred in higher-income neighborhoods (odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.70, 0.96) and more likely to have occurred in fragmented neighborhoods (OR = 1.35; 95% CI = 1.05, 1.72). They were more likely than heroin overdose fatalities to have occurred in higher-income (OR = 1.31; 95% CI = 1.12, 1.54) and less fragmented (OR = 0.71; 95% CI = 0.55, 0.92) neighborhoods. Conclusions. Analgesic overdose fatalities exhibit spatial patterns that are distinct from those of heroin and nonoverdose unintentional fatalities. Whereas analgesic fatalities typically occur in lower-income, more fragmented neighborhoods than nonoverdose fatalities, they tend to occur in higher-income, less unequal, and less fragmented neighborhoods than heroin fatalities.