Background: QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) is a methodology previously developed to extract pesticides from vegetables and fruits and has been fully applied for different analytical approaches.Objective: In the present study, a rapid and less laborious modified QuEChERS extraction method for the quantification of 13 opioids [codeine, morphine, heroin, 6-acetylmorphine (6-AM), desomorphine, ethylmorphine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 2-ethyl-5-methyl-3,3- diphenyl-1-pyrroline (EMDP), papaverine, tramadol, O-desmetyltramadol (M1) and, tapentadol], cocaine and cocaethylene in whole blood was developed and validated by Gas Chromatography-Mass Spectrometry. Method: The modification of QuEChERS method consisted in the pretreatment of the whole blood samples using ultrasonication, the use of ethyl acetate as extraction solvent and a previous step of sample alcalinization. The use of dispersive separation steps such as Dispersive Solid-Phase Extraction (dSPE) or sorbents such as Primary Secondary Amine (PSA) was suppressed to minimize the errors and, to improve the velocity of the analysis. Results: The method proved to be selective and the regression analysis for the analytes was linear in the range of 31.2-2000 ng/mL with correlation coefficients > 0.98. The coefficients of variation did not exceed 15%. The lowest limit of detection and quantification for all the analytes were below the therapeutic range of the drugs. The recoveries of the analytes ranged from 52.4 to 95.0%. Conclusion: The developed method can provide a rapid, effective and “greener” process for the analysis of a wide range of opioids drugs in whole blood samples and can be applied to clinical and forensic antemortem and postmortem cases.