Objectives: To use logistic regression modeling to identify factors associated with high self-efficacy for sexual negotiation and condom use in a sample of South African youth. Methods: The Reproductive Health and HIV Research Unit (RHRU) National Youth Survey examined a nationally representative sample of 7409 sexually active South African youth aged 15 to 24 years. We used logistic regression modeling in this sample to identify factors associated with the main outcome of high self-efficacy. Results: Among female respondents (n = 3890), factors associated with high self-efficacy in the adjusted model were knowing how to avoid HIV (odds ratio [OR] = 2.30, 95% confidence interval [CI]: 1.05 to 5.00), having spoken with someone other than a parent or guardian about HIV/AIDS (OR = 1.46, 95% CI: 1.01 to 2.10), and having life goals (OR = 1.28, 95% CI: 1.10 to 1.48). Not using condoms during their first sexual encounter (OR = 0.61, 95% CI: 0.50 to 0.76), a history of unwanted sex (OR = 0.66, 95% CI: 0.51 to 0.86), and believing that condom use implies distrust in one's partner (OR = 0.57, 95% CI: 0.51 to 0.86) were factors associated with low self-efficacy among female respondents. Male respondents (n = 3519) with high self-efficacy were more likely to take HIV seriously (OR = 4.03, 95% CI: 1.55 to 10.52), to believe they are not at risk for HIV (OR = 1.38, 95% CI: 1.12 to 1.70), to report that getting condoms is easy (OR = 1.85, 95% CI: 1.23 to 2.77), and to have life goals (OR = 1.30, 95% CI: 1.10 to 1.54). Not using condoms during their first sexual experience (OR = 0.51, 95% CI: 0.39 to 0.67), a history of having unwanted sex (OR = 0.47, 95% CI: 0.34 to 0.64), believing condom use is a sign of not trusting one's partner (OR = 0.63, 95% CI: 0.46 to 0.87), and refusing to be friends with HIV-infected persons (OR = 0.52, 95% CI: 0.32 to 0.85) were factors associated with low self-efficacy among male respondents in the fully adjusted model. Conclusions: We used the social cognitive model (SCM) to identify factors associated with self-efficacy for condom use and sexual negotiation. Many of these factors are modifiable and suggest potential ways to improve self-efficacy and reduce HIV sexual risk behavior in South African youth.