All NSAIDs may induce cardiotoxicity. In this respect naproxen is relatively the safest choice. Selective cyclo-oxygenase-2-inhibitors (coxibs) are at least as effective in preventing clinically relevant gastrointestinal toxicity as non-selective NSAIDs plus a protonpump inhibitor (PPI). Non-selective NSAIDs plus a PPI are more effective in prevention of dyspepsia than coxibs. After a serious gastrointestinal complication while using NSAIDs, in principal the patient should no longer use NSAIDs. If needed, a coxib plus a PPI is the first choice.