Background Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes. Methods In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969. Findings We recorded significant differences between treatment groups in diastolic blood pressure (1·91 [95% CI −2·88 to −0·94] mm Hg, p=0·0001) and mean arterial pressure (1·36 [−2·49 to −0·23] mm Hg, p=0·0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0·03 [−0·04 to 0·11] mmol/L), systolic blood pressure (−0·33 [−2·41 to 1·75] mm Hg), or HbA1c (−0·15% [−0·33 to 0·03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio £28 933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4·9 (95% CI 4·0–5·9) mm Hg, 3·8 (3·2–4·4) mm Hg, and 0·45 (0·40–0·51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0·04% [−0·04 to 0·13]), p=0·290). Interpretation We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes. Funding Pfizer, Sanofi-Aventis, Servier Laboratories UK, Merck Sharp & Dohme/Schering-Plough, Takeda UK, Roche, Merck Pharma, Daiichi-Sankyo UK, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bristol-Myers Squibb, Solvay Health Care, and Assurance Medical Society UK.