Emulated trial design, to compare rates of major adverse cardiovascular events among diclofenac initiators with rates among non-initiators or initiators of active comparator drugs in Denmark. Individual level linkage of nationwide population based registries was used to emulate the eligibility criteria, washout period, treatment groups, and follow-up period of a clinical controlled trial. Eligible individuals were aged at least 18 years who had at least one year of prescription history and none of the exclusion criteria. All initiators of diclofenac and naproxen were identified during the month of January 1996. Each person was followed up to a non-fatal endpoint, death, loss to follow-up, or 30 days of follow-up. Enrolment was repeated in the months of February and March, and subsequently for every month up to December 2016. The series of 252 emulated trials were then statistically pooled into one model, generating a sample size of 1 370 832 diclofenac initiators and 291 490 naproxen initiators. A similar approach was used to identify ibuprofen initiators (n=3 878 454) and propensity score matched initiators of paracetamol (n=764 781) and NSAID non-initiators (n=1 303 209). B=baseline; MACE=major adverse cardiovascular events; D=death or emigration; F=30 days of follow-up