BACKGROUND In South Africa, the risk factors for cardiovascular disease (CVD) are increasing, thereby impacting patients with drug-resistant tuberculosis (DR-TB). OBJECTIVE To determine the prevalence of traditional CVD risk factors (diabetes mellitus [DM], smoking, hypertension, increased body mass index [BMI]) and a total risk score for CVD among patients with DR-TB. METHODS This cross-sectional study was nested within an ongoing cluster-randomized trial in 10 DR-TB hospitals in South Africa. The data for the present study were collected between November 2014 and July 2016. RESULTS Of 900 participants aged 18 years, 75.1% were co-infected with the human immunodeficiency virus (HIV), and 52.3% had one or more CVD risk factors. The prevalence of CVD risk factors was hypertension (16.7%), increased BMI (16.6%), DM (5.2%), and smoking (31.4%). Among patients with DM or hypertension, 58.8-95.5% had additional comorbid CVD risk factors. Of 398 participants eligible for the CVD risk score (age 35 years), 23.4% had a moderate or high CVD risk score. CONCLUSION Patients with multiple diseases, including DR-TB and HIV, with traditional CVD risk factors, may have higher risks for negative outcomes during treatment for DR-TB. TB providers should identify people at risk to initiate primary and secondary prevention to improve outcomes. .