Background: Primary prevention of cardiovascular disease (CVD) requires adequate control of hypertension and diabetes. We designed and implemented pharmaceutical and healthy lifestyle interventions for patients with diabetes and/or hypertension in rural primary care, and assessed their effectiveness at reducing the rate of severe CVD events. Methods: We used a pragmatic, parallel group, two-arm, controlled, superiority, cluster trial design. We randomised 67 township hospitals from rural Zhejiang province, China, to intervention (34) or control (33) arms. Using health records, we recruited patients with hypertension and a 10-year CVD risk of 20% or higher and all patients with type 2 diabetes. The intervention included prescription of a standardised package of medicines, individual advice on lifestyle change and adherence support. Control was usual hypertension and diabetes care. In both arms, as usual in China, most outpatient drug costs were out-of-pocket. The primary outcome was severe CVD events after 36 months of intervention, as recorded by the CVD surveillance system. Findings: We conducted the trial from December 2013 until May 2017. We randomly allocated 13,385 and 14,745 participants to the intervention and control arms respectively. At 36 months there were 762 and 874 severe CVD events in the intervention and control arms respectively (incidence rate = 1.92 and 2.01 per 100 person-years respectively; crude incidence rate ratio = 0.90 [95% CI: 0.74, 1.08; P = 0.259]). Self-reported adherence to recommended medicines was significantly higher in the intervention arm, but adherence was low. Differences in mean blood pressure were significant but small. No safety concerns were identified. Interpretation: The comprehensive package of pharmaceutical and healthy lifestyle interventions did not significantly reduce severe CVD events over 36 months. Improving health system factors such as universal coverage for the cost of essential medicines are required for successful risk-based CVD prevention programmes. Trial Registration: Current Controlled Trials (ISRCTN58988083). Funding: UK DFID (COMDIS-HSD) and Zhejiang Health Bureau.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: Ethics approval was obtained from the University of Leeds School of Medicine Research Ethics Committee (reference HSLTLM/12/010) and the Ethics Committee of Zhejiang Provincial Centre for Disease Control and Prevention, China (reference 18/06/2012). Written informed consent was obtained from both hospital directors and all participating individuals.