The first large-scale assessment of pharmaceuticals in drinking water in the Czech Republic (CR) focused on the detection of five substances. Samples were collected from public water systems supplying 5.3 million people, 50.5% of the Czech population. In the initial survey of tap water from 92 major supply zones using mostly surface water, no pharmaceutical exceeded the limit of quantification (LOQ = 0.5 ng/L). In a second survey, samples were collected from the outlet of 23 water treatment plants (WTPs) considered of high risk because they use surface waters influenced by wastewater. Ibuprofen was the most frequently found pharmaceutical (19 samples), followed by carbamazepine (12), naproxen (8), and diclofenac (3); concentrations ranged from 0.5 to 20.7 ng/L, with medians below 6 ng/L. Concentrations of 17α-ethinylestradiol were below the LOQ. A follow-up survey included tap and outlet samples from eight of the 23 WTPs with the highest concentrations. Pharmaceuticals were quantified in only three tap water samples. Regarding risks to consumers, these results suggest that a relatively small population (<10%) in the CR is exposed to quantifiable concentrations of pharmaceuticals in tap water and that an extremely high margin of safety (several thousand-fold to several million-fold) is associated with these exposures.