A robust, credible, and practical multiresidue method based on liquid chromatography/tandem/mass spectrometry (LC/MS/MS) was developed for the simultaneous determination of 9 macrocyclic lactone drugs (abamectin B1a, doramectin, erythromycin, ivermectin B1a, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin A) in bovine, porcine, chicken, and sheep muscles. The drugs were extracted with acetonitrile, and the extracts were defatted with n-hexane and further cleaned up on a C18 solid-phase extraction cartridge. LC/MS/MS data acquisition was achieved by using the multiple-reaction monitoring (MRM) mode, i.e., 2 transitions, to provide a high degree of sensitivity and repeatability. Matrix-matched standard calibration curves were used to achieve the best accuracy of the method by compensating for the matrix effect. The calibration graphs were linear (r > 0.998) from 10 to 1000 ng/mL for erythromycin, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin, and from 5 to 250 ng/mL for abamectin, doramectin, and ivermectin. The average recoveries of the 9 drugs were between 64.5 and 105%, calculated by using matrix-matched calibration, with relative standard deviation values ranging from 1.6 to 14%. The limits of detection were 0.1 microg/kg for erythromycin, josamycin, roxithromycin, and tylosin; 0.2 microg/kg for tilmicosin and kitasamycin; and 0.5 microg/kg for abamectin, doramectin, and ivermectin. For confirmation, the MRM ratios for the 9 drug residues in the samples and the solvent were evaluated and found to be within the ratio criteria set by the guidelines of the European Union.