Introduction <p>It is uncertain whether the relative increase in cardiovascular risk associated with non-steroidal anti-inflammatory drug (NSAID) use differs according to hypertension status.</p> Objective <p>The aim of this study was to investigate the association between NSAID use and major adverse cardiovascular events (MACE) in individuals with never, former, and current hypertension.</p> Methods <p>We conducted a case-crossover study including all first-time respondents to the Danish National Health Surveys of 2010, 2013, or 2017, without prior cardiovascular disease, who experienced a MACE from survey completion through 2021. We defined MACE as a composite of myocardial infarction, ischemic stroke, heart failure, atrial fibrillation or flutter, and cardiovascular death. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between use of ibuprofen, naproxen, or diclofenac and MACE, and stratified the analyses by hypertension status (never, former, or current). We obtained information on NSAID use and MACE from nationwide Danish health registries.</p> Results <p>When comparing ibuprofen use with non-use, the ORs (95% CI) were 1.31 (1.13–1.52) for never hypertension, 1.85 (1.32–2.57) for former hypertension, and 1.39 (1.17–1.65) for current hypertension. For naproxen, ORs were 1.51 (0.71–3.23) for never hypertension, 1.96 (0.54–7.17) for former hypertension, and 2.35 (1.16–4.74) for current hypertension. For diclofenac, ORs were 1.48 (0.84–2.60) for never hypertension, 1.84 (0.53–6.37) for former hypertension, and 1.50 (0.82–2.74) for current hypertension.</p> Conclusions <p>The NSAID use-associated cardiovascular risk was not modified by hypertension status.</p>