BACKGROUND Atrial fibrillation (AF) is a common condition, associated with raised mortality and risk of major morbidity, and is predicted to increase due to an aging population. AIM To update earlier research of AF predictors using UK data. DESIGN AND SETTING Case-control analysis of adults aged 18 years and older with a diagnosis of AF in practices registered with the General Practice Research Database (GPRD) in the UK. METHOD Using the GPRD, a case.control analysis was performed using logistic regression to compare 55,412 incident AF cases to 216,400 controls, for medical history and prior use of drugs. The association between time since start of diagnosis or drug use and AF risk was summarised using Spline regression. RESULTS The following were confirmed as risk factors for AF: heart failure (risk ratio [RR] 2.91 [95% CI = 2.59 to 3.27]); ischaemic heart disease (IHD) (RR 2.00 [95% CI = 1.78 to 2.24]); hypertension (RR 2.60 [95% CI = 2.32 to 2.92]); hyperthyroidism (RR 1.56 [95% CI = 1.39 to 1.75]); being a heavy drinker (RR 1.43 [95% CI = 1.27 to 1.60]); cerebrovascular accident (RR 1.48 [95% CI = 1.32 to 1.66]); and obesity (body mass index ≥30 kg/m(2) RR 1.29 [95% CI = 1.15 to 1.45]). Current use of oral glucocorticoids (RR 1.62 [95% CI = 1.44 to 1.82]) and of beta-2 agonists (RR 1.30 [95% CI = 1.16 to 1.46]) were identified as significant risk factors, and statins (RR 0.82 [95% CI = 0.73 to 0.92]) as a significant protective factor. No effect was found for current use of bisphosphonates (RR 0.95 [95% CI = 0.85 to 1.07]), renin.angiotensin.aldosterone system (RAAS) agents (RR 1.04 [95% CI = 0.93 to 1.17]), or xanthine derivatives (RR 1.09 [95% CI = 0.97 to 1.22]). Spline regression analysis found the effect of heart failure, IHD, use of oral glucocorticoids, and use of statins on the likelihood of developing AF was sustained over a number of years. CONCLUSION These findings update the risk factors that are associated with AF, and confirm the protective properties of statins and the risks of beta-2 agonists in developing AF, but not the supposed protective qualities of glucocorticoids and RAAS agents.