Aims: Non-steroidal anti-inflammatory drugs (NSAIDs), particularly selective COX-2 inhibitors, are associated with an increased risk of cardiovascular adverse events. However, the association between these drugs and out-of-hospital cardiac arrest wth electrocardiogram-documented ventricular tachycardia/ventricular fibrillation (VT/VF-OHCA) has not been studied yet. This study was aimed to evaluate the association between the use of selective COX-2 inhibitors or conventional NSAIDs and VT/VF-OHCA compared with non-use. Methods and results: A case-control study was conducted among 2483 cases with VT/VF-OHCA from the AmsteRdam REsuscitation STudies (ARREST) registry, an ongoing Dutch registry of OHCA, and 10 441 non-VT/VF-OHCA-controls from the Dutch PHARMO Database Network, containing drug dispensing records of community pharmacies, over the period July 2005-December 2011. Up to five controls were matched for age and sex to one case at the date of VT/VF-OHCA (index date). Odds ratios (ORs) and 95%confidence intervals (CIs) were calculated by conditional logistic regression analysis. Of the cases, 0.5% was currently exposed at the index date to selective COX-2 inhibitors and 2.5% to conventional NSAIDs. Neither current use of selective COX-2 inhibitors nor conventional NSAIDs were associated with an increased risk of VT/VF-OHCA (adjusted OR 1.11, 95% CI: 0.79-1.56 and adjusted OR 0.97, 95% CI: 0.86-1.10, respectively) compared with non-use. Stratification for VT/VF-OHCA with presence/absence ofacute myocardial infarction did not change these results. Conclusion: Exposure to selective COX-2 inhibitors or conventional NSAIDs was not associated with an increased risk of VT/VF-OHCA compared with non-use.