Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. 37 variant TPMT-encoding alleles have been discovered so far. These variants produce enzyme with reduced enzymatic activity. Wild-type enzyme is denoted TPMT*1/*1, while variants were given numbers successively as they were discovered. The latest variant, TPMT*37, was discovered in 2014. The most common variant alleles of TPMT gene are: TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. Patients who are heterozygous for the enzyme, should have a thiopurine drug dose reduction, while homozygous patients should either stay free of this drug, or should have up to 10x drug dose reduction. Furthermore, blood parameters should be checked regularly. According to early studies of this enzyme, variant homozygosity is present in 1/300 persons; however – further population studies have revealed different ratios in Caucasian, Asiatic and African population. The first aim of this study was to investigate frequencies of the most common variant alleles in Croatian inflammatory bowel disease (IBD) patients and in healthy individuals. 685 participants are included, out of whom 459 are IBD patients (338 Crohn’s disease patients and 221 ulcerative colitis patients) and 226 are healthy volunteers. 94.55% IBD of patients and 94.25% of healthy volunteers have homozygous wild-type enzyme (TPMT*1/*1). TPMT*1/*2 and TPMT*1/*3C are present in 0.87% and 1.53% IBD patients, respectively; these variants are not present in healthy volunteers. TPMT*1/*3A is present in 3.05% IBD patients and 5.75% healthy volunteers. TPMT*3B allele is not found in any group. Variant genotypes are statistically significantly more common in Crohn's disease than in ulcerative colitis subgroup (p=0.032). We also compared frequencies of variant TPMT alleles in our population to selected countries which had had results published earlier. We found the overall frequency of variant alleles in our population statistically nonsignificantly lower when compared with other populations of Caucasian origin. Azathioprine is a thiopurine drug registered in IBD treatment in Croatia. Patients who have variant TPMT genotype, i.e. reduced enzyme activity, possibly develop severe adverse effects. The most common azathioprine adverse effect is myelotoxicity. Additionaly, concomitant therapy possibly influences adverse effects occurrence. Regarding aforementioned, the other aim of the study was to investigate a relationship between the most common TPMT polymorphisms, AZA adverse effects and concomitant therapy that is regularly applied in IBD. Out of 263 patients treated with AZA, 64 have developed adverse effects (24%). The most common adverse effects is myelotoxicity, with thrombocytopenia slightly more prevalent than leukopenia. The most common toxic hepatic manifestation is diffuse liver lesion, while pancreatic toxicity usually presents with acute pancreatitis. The majority of adverse effects occurs in patients with wild-type genotype. Statistical analysis shows that only TPMT genotype influences adverse effects occurrence (p=0.0038), notably TPMT*3A variant (p=0.0036). There is no influence of concomitant therapy – either aminosalicylate, corticosteroid or anti-TNF – on AZA-related toxicity.