BACKGROUND: Natrelle 410 silicone breast implants are approved in the United States for breast augmentation, reconstruction, and revision. METHODS: In two ongoing, prospective, multicenter 10-year studies, 17,656 subjects received Natrelle 410 implants for augmentation (n = 5059), revision-augmentation (n = 2632), reconstruction (n = 7502), or revision-reconstruction (n = 2463). Capsular contracture, implant malposition, and late seroma were documented. Cox proportional hazards regression analyses evaluated potential associations between subject-, implant-, and surgery-related factors and these complications. RESULTS: Median follow-up was 4.1, 2.6, 2.1, and 2.3 years in the augmentation, revision-augmentation, reconstruction, and revision-reconstruction cohorts, respectively. Incidence of capsular contracture across cohorts ranged from 2.3 to 4.1 percent; malposition, 1.5 to 2.7 percent; and late seroma, 0.1 to 0.2 percent. Significant risk factors for capsular contracture were subglandular implant placement, periareolar incision site, and older device age in the augmentation cohort (p < 0.0001), older subject age in the revision-augmentation cohort (p < 0.0001), and higher body mass index (p = 0.0026) and no povidone-iodine pocket irrigation (p = 0.0006) in the reconstruction cohort. Significant risk factors for malposition were longer incision size in the augmentation cohort (p = 0.0003), capsulectomy at the time of implantation in the reconstruction cohort (p = 0.0028), and implantations performed in physicians' offices versus hospitals or standalone surgical facilities in both revision cohorts (p < 0.0001). The incidence of late seroma was too low to perform risk factor analysis. CONCLUSIONS: These data reaffirm the safety of Natrelle 410 implants. Knowledge of risk factors for capsular contracture and implant malposition offers guidance for reducing complications and optimizing outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.