Sexually transmitted disease (STD) patients are more likely to experience a future STD including human immunodeficiency virus (HIV). The aim of this study was to examine the efficacy of behavioral interventions to reduce sexual risk behavior and incident STDs among patients attending STD clinics in the United States. A meta-analysis of 32 studies with 48 separate interventions targeting STD patients (N = 67,538) was conducted. Independent raters coded study, sample, and intervention characteristics. Effect sizes, using both fixed- and random-effects models, were calculated. Potential moderators of intervention efficacy were assessed. Relative to controls, intervention participants increased their condom use and had fewer incident STDs, including HIV, across assessment intervals (d (+)s ranging from 0.05 to 0.64). Several sample (e.g., age and ethnicity) and intervention features (e.g., targeting intervention to a specific group) moderated the efficacy of the intervention. Behavioral interventions targeted to STD clinic patients reduce sexual risk behavior and prevent HIV/STDs. Widespread use of behavioral interventions in STD clinics should be a public health priority.