The aim was to identify and quantify the association between the use of particular medications during the first trimester of pregnancy and selected congenital abnormalities (CAs) of newborns. Data were from the Czech National Registry of CAs. We used a case-control design, and collected total of 7285 cases and 9143 controls. Thiethylperazine and iron compounds had no effect on development of CAs. Lower odds ratio and potentially protective associations were found between CAs and bioflavonoids, folic acid, progesterone, levothyroxine, and iodine therapy. Since the protective effect of bioflavonoids was not described before, analysis of interaction with other drugs was performed. However, their protective effect was not confirmed and the strongest significant protective effect was detected in combination of bioflavonoids and progesterone. Increased odds ratio were identified for hydroxyprogesterone, phenoxymethylpenicillin, aspirin, paracetamol and valproic acid. The association between paracetamol and congenital foot deformities was not significant, while the same association for the whole group of CAs and deformities of musculoskeletal system had significantly increased odds ratio. Except newly described effect of bioflavonoids, our results are in agreement with risk categories defined by health authorities in USA and Australia, and with results of other studies. According to our results, paracetamol does not influence development of congenital foot deformities.