Introduction: Drug checking as a part of drug harm-reduction strategies represents an essential aspect of public health policies. It focuses on rapid identification of drugs that individuals intend to use during night events, in order to implement health-protective behaviors. Chemical drug analysis techniques vary considerably, from simple colorimetric reagents to advanced forensic methods such as gas chromatography/mass spectrometry (GC/MS).Materials and Methods: In 2019, drug-check services were offered at some night events in Umbria (Central Italy). One hundred and twenty attendees directly delivered unidentified substances to a harm-reduction worker, who collected a few milligrams of the substances on ceramic plates and added a drop of colorimetric reagent. Multiple reagents were used to increase the diagnostic capacity of a substance, which may react with a specific drug or a few drugs. Later, a fraction of the samples was analyzed by GC/MS. The concordance of the results obtained using these two methodologies and the intended behaviors of consumers after being informed of the test result was evaluated.Results: We analyzed 120 samples by colorimetric test: 32 MDMA, 25 ketamine, 10 amphetamine, 11 cocaine, 8 heroin, and 4 LSD samples. The results were inconclusive for 29 samples. The GS/MS analysis confirmed MDMA in 84%, ketamine in 78%, amphetamine in 91%, cocaine in 92%, heroin in 88%, and LSD in 100% of the samples. The results of samples with inconclusive results were as follows: 2, MDMA; 7, ketamine; 2, amphetamine; 2, cocaine; 2, heroin; 2, mephedrone; 6, mixes; 1, debris; and 5, adulterants as the main component. Twenty-one of 29 participants reported that they had no intention of consuming the unidentified substance.Discussion: The high percentage of individuals who claimed no intention of consuming the unidentified drugs indicates that drug checking is viable as a part of drug harm-reduction strategies. Overall, colorimetric reagents showed a good performance with regard to samples being unadulterated (LSD) or minimal in quantity, but failed to identify mixtures of substances and the adulterants present in them. Therefore, the use of more discriminatory on-site methods such as Raman or infrared spectrometry is strongly recommended.