Purpose Interpretation of drug levels in decomposed and buried corpses is difficult. We aimed to determine postmortem distribution of drugs in putrefied-decomposed visceral tissues and buried bones, and the effect of decomposition and burial on distribution of drugs in organs and bone tissues by administering drug groups selected from various drug classes to domestic pigs. Methods Pigs were divided into groups (n = 5) and dosed with a variety of drugs. Peripheral blood, organ and bone samples in different anatomical locations were collected from pigs killed. Organ samples were collected at postmortem 4th, 24th, 48th, 72nd and 96th hour. Then the corpses were buried below soil ground. Bone samples from buried corpses were collected at 5th and 10th months of the burial time by exhumation. All samples were analysed using liquid chromatography-tandem mass spectrometry after making sample preparation using appropriate methods. Results Only 10 of the 14 drugs were detected in the initial peripheral blood. For all bone types analyzed, highest drug levels were detected at thorax region and lowest drug levels were detected at the lower extremity. Given the fact that most of the soft tissue is located in the thorax region, it is possible that during the decomposition process, drugs partitioned from the liquefied tissue into bones. That the drug levels in bones decreased was observed when exhumation was done at 10th month of the burial time. Conclusions Drug distribution in organ and bone of decomposed and burial corpses vary due to unknown mechanisms and completely unexplained conditions such as postmortem redistribution.