Abstract: To determine the trace organic sulfides in mainstream cigarette smoke with high accuracy, a simultaneous analytical method was developed using a blowback system coupled with gas chromatography-tandem mass spectrometry (GC-MS-MS) to quantify 35 potential organic sulfides in mainstream cigarette smoke, with optimized pretreatment conditions and the time of blowback in the instrumental parameters. This method was then used to analyze the releases of 35 organic sulfides in 32 Virginia type and 6 blended type cigarette samples and the differences among them. The results showed that: 1) The introduction of the blowback system significantly reduced the retention of high boiling point components in the chromatographic separation columns, lowered the risk of cross contamination across samples, and enhanced the retention time consistency during continuous injections. 2) A total of 25 organic sulfides were detected in mainstream smoke of the cigarette samples, and 19 of which were identified in all the samples. The results of principal component analysis (PCA) showed that there was clear distinction between the two types of cigarettes. Heatmap analysis and t-test results revealed that the average releases per unit tar of thiophene, thiazole, furfuryl mercaptan, tetrahydrothiophen-3-one, 2-acetylthiazole, 4-methyl-5-vinylthiazole, 5-methylthiophene-2-carboxaldehyde and 5-(2-hydroxyethyl)-4- methylthiazole were significantly higher in mainstream smoke of blended type cigarettes than those in Virginia type cigarettes (p < 0.01), while the average release per unit tar of 4-(methylthio)butyronitrile in mainstream smoke of Virginia type cigarettes was 2.9 times of that in blended cigarettes (p < 0.01). 3) Six organic sulfides were detected only in mainstream smoke of some cigarette samples, with the detection rates of methyl 2-thiofuroate and 2-methyl-3-methylthiopyrazine in mainstream smoke of blended cigarette samples reached 67% and 83% respectively, and those of furfuryl methyl disulfide, dibutyl sulfide, 8-mercaptomenthone and difurfuryl sulfide in mainstream smoke of cigarette samples were no more than 40%.