Traditionally agrochemical residues in tobacco have been analyzed with multi-residue methods by using gas chromatography with either selective detectors (ECD, NPD, FPD) or mass spectrometry. Because many modern agrochemicals are either not amenable to GC or not detectable at sufficiently low levels, more rapid and sensitive analytical methods are needed to quantify the residues. This study was carried out for two main purposes: to give a more rapid and accurate sample preparation, and to use the high selectivity and sensitivity of analyte detection by triple quadrupole mass spectrometry (MS/MS). We compared the three sample preparation methods of agrochemical residues in tobacco such as the conventional liquid-liquid extraction (LLE), pressurized liquid extraction (PLE) and QuEChERS (quick, easy, cheap, effective, rugged and safe) methods. These methods were validated for listed agrochemicals in the CORESTA ACAC guide that were amenable to GC-MS/MS determination. LLE with acetonitrile, and PLE with acetone were followed by solid phase extraction (SPE), the SPE fractions were analyzed by GC-MS/MS in CI and EI mode. In the QuEChERS method, the effects of adsorbent and analyte dependent matrix for the tobacco types were investigated. MS/MS acquisition provided higher specificity and selectivity for agrochemicals and lower limit of detection and quantification than selective detectors and MS. The QuEChERS method did not need a complex clean-up procedure and can be used for the rapid and sensitive analysis of agrochemicals and as an alternative to LLE and PLE methods.