Aims: To examine whether the blood pressure (BP) profiles of lumiracoxib and high-dose ibuprofen differed in patients treated with different classes of antihypertensive medications. Methods: A 4-week, multicentre, randomised, double-blind study has compared the effects of lumiracoxib 100 mg once daily (od) (n = 394) and ibuprofen 600 mg three times daily (tid) (n = 393) on ambulatory BP in osteoarthritis (OA) patients with controlled hypertension. Here, we present subgroup analyses for patients receiving different antihypertensive classes. The primary outcome was a comparison of the change in 24-h mean systolic ambulatory BP (MSABP) from baseline to week 4. Patients receiving angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) represented the largest subgroups receiving antihypertensive monotherapy. Results: For patients receiving an ARB monotherapy, the least squares mean (LSM) 24-h MSABP at week 4 fell with lumiracoxib 100 mg od and increased with ibuprofen 600 mg tid, creating an estimated treatment difference of 8.1 mmHg in favour of lumiracoxib (p <0.001). For patients receiving an ACEI and a beta-blocker monotherapy, the estimated treatment difference was 8.2 mmHg (p <0.001) and 5.8 mmHg (p = 0.002) in favour of lumiracoxib respectively. These treatment differences were greater than observed in the overall population (5.0 mmHg in favour of lumiracoxib). In patients receiving diuretics or calcium channel blockers, treatment differences in MSABP were smaller and not statistically significant, although they remained in favour of lumiracoxib. Conclusion: Lumiracoxib 100 mg od resulted in less destabilisation of BP than high-dose ibuprofen 600 mg tid, and this effect was the greatest in subgroups treated with drugs blocking the renin-angiotensin system.