Introduction The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled. Methods We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157; apnea hyponea index [AHI]: 14.7 (7.2–33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P<0.05 was considered significant. Results Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP > = 4hours/night. Conclusion We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910.