The study's objective was to assess the role of toxicological screening by high performance liquid chromatography with diode array detection (HPLC-DAD) in diagnosis of drug intoxication to compare those results with results obtained by immunoassay and colorimetric tests. This prospective study was carried out over a period of one year (2012) at the Laboratory of Moroccan Poison Control and Pharmacovigilance Center. Toxicological screening was performed by using HPLC-DAD, immunoassay and colorimetric tests using plasma and urine of 107 patients. The plasma sample was submitted to a liquid-liquid extraction. The residue was subjected to HPLC-DAD using prazepam as the internal standard. The separation was carried out on an ODS-Hypersil column with phosphate buffer /acetonitrile as the mobile phase. The screening immunoassay and colorimetric tests have been applied to urine samples. The most common drugs present were benzodiazepines (39, 44%) and antidepressants (23, 94%). The results showed a good agreement (67.29 %) between the results of screening by HPLC-DAD and results obtained by immunoassay and colorimetric tests. The discordance was occurred in 32.71%. In our study, the causes of discordance were technical limits. It was the absence of the molecule suspected at the spectral library or the similarity of the UV-spectra. In other cases the toxicokinetic of the suspected substance influence the results; the compound is metabolized or even eliminated or the identified drug is administered to the patient as symptomatic treatment. Data analysis shows that toxicological screening by HPLC -DAD allows the identification of unrecognized drugs by immunoassay and colorimetric tests. This method can simultaneously identify several molecules belonging to different classes of drugs.