Abstract A sample of 301 Philadelphia adolescents were assessed for substance use and place-based social network quality, a weighted variable based upon risky and protective behaviors of alters. The network measure was anchored in routine locations identified as safe, risky, important, or favorite. Results show young females' (13–16) substance use was strongly associated with their place-based social networks compared to older females (17–20) and compared to young and older males. Younger females' protective networks reduced their likelihood of substance use compared to females with risky networks (OR = .94, CI = .89–.99, p < .05), while young males experienced no protective network effects. Older females' protective networks reduced the likelihood of substance use compared to those with risky networks (OR = .96, CI = .93–.99, p < .005). Older males' protective networks also reduced their likelihood of substance use (OR = .86, CI = .74–.99, p < .05). Results highlight the varying affects of place, gender, and age on adolescent social network protection and associated risk for substance use.