Summary: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used and highly effective in the treatment of many com-mon inflammatory diseases and pain. However, they can also worsen cardiovascular risk, which is one of the most important adverse effects, directly associated with cyclooxygenase (COX) inhibition ‒ the NSAIDsʼ mechanism of action. Anti-inflamma-tory and pain treatment is frequently required in elderly pa-tients with many concomitant chronic diseases, among which cardiovascular disorders are the most common. Appropriate NSAID administration needs special attention and thorough assessment of the cardiological and gastroenterological risk as well as pharmacological features. NSAIDs acting on COX-2 with higher affinity than on COX-1 are characterized by a bet-ter gastrointestinal safety profile and have been shown to be non-inferior in cardiovascular risk when compared with non-selective NSAIDs. Properly prescribed NSAID therapy may be beneficial in improving quality of life, especially in patients with chronic severe inflammation.