The paper present discussion of the risks of adverse events development in elderly patients with comorbid pathology, arising against the background of long‑term use of non‑steroidal anti‑inflammatory drugs (NSAIDs) for the relief of pain and inflammatory articular syndromes in combination with medications of other pharmaceutical groups (in particular acetylsalicylic acid and antiplatelet agents) used to treat concomitant diseases. The NSAIDs‑induced adverse events mostly often develop and have mostly intensive manifestations in the gastroduodenal zone. They are presented as clinical variants of NSAID‑induced gastropathies, including the forms of erosive and ulcerative lesions. When choosing NSAIDs for the treatment of elderly patients, especially with comorbid pathology, it is necessary to analyze risk factors, contributing to the development of adverse events, namely the gender and age of a patient, the presence of peptic ulcer and its complications in the anamnesis, H. pylori infection, the range of drugs taken, doses and duration of taking NSAIDs, their selectivity, combination with other drugs that have similar adverse effects on the mucous membranes of the gastrointestinal tract. Long‑term use of NSAIDs, in addition to undesirable gastrointestinal side effects, can lead to destabilization of arterial hypertension and heart failure, increase the risk of cardiovascular accidents, cause nephro‑ and hepatotoxic effects, hematological complications, allergic skin reactions and bronchospasm, the development of other adverse events. Based on a clinical example, a strategy for the prevention and treatment of NSAID gastropathy is proposed, caused by long‑term use of a combination of drugs that have an unfavorable effect on the gastroduodenal mucosa. The high clinical effectiveness has been demonstrated for the treatment regimen using pantoprazole as a representative of proton pump inhibitors with the longest acid‑suppressive effect and a low potential for adverse drug‑drug interactions in combination with colloidal bismuth subcitrate, which has a pronounced cytoprotective effect on the gastroduodenal mucosa. It can be recommended for elderly patients with comorbid pathology for prevention and treatment of NSAID‑induced gastropathies.