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To enhance the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of essential medications used to treat acute and chronic pain, is an important and urgent task. For its solution, in 2015 Russian experts provided an NSAID selection algorithm based on the assessment of risk factors (RFs) for drug-induced complications and on the prescription of drugs with the least negative effect on the gastrointestinal tract and cardiovascular system. The PRINCIPLE project was implemented to test the effectiveness of this algorithm.Subjects and methods. A study group consisted of 439 patients (65% were women and 35% – men; their mean age was 51.3±14.4 years) with severe musculoskeletal pain, who were prescribed NSAIDs by using the above algorithm. The majority of patients were noted to have RFs: gastrointestinal and cardiovascular ones in 62 and 88% of the patients, respectively. Given the RF, eight NSAIDs were used; these were aceclofenac, diclofenac, ibuprofen, ketoprofen, meloxicam, naproxen, nimesulide, and celecoxib, the latter being prescribed most commonly (in 57.4% of cases). NSAID was used in combination with proton pump inhibitors in 30.2% of the patients. The follow-up period was 28 days. The investigators evaluated the efficacy of therapy (pain changes on a 10-point numeric rating scale (NRS)) and the development of adverse events (AE). Results and discussion. Pain was completely relieved in the overwhelming majority (94.9%) of patients. There were no significant differences in the efficacy of different NSAIDs according to NRS scores. The number of AE was minimal and did not differ between different NSAIDs, with the exception of a higher frequency of dyspepsia caused by diclofenac (15.7%). There were no serious complications or therapy discontinuation because of AE.Conclusion. The use of the NSAID selection algorithm allows for effective and relatively safe therapy with these drugs in real clinical practice.