The cost of HIV preexposure prophylaxis (PrEP) medication and care is a key barrier to PrEP use. Using population-based surveys and published information, we estimated the number of people with uncovered costs for PrEP care among US adults with PrEP indications, stratified by HIV transmission risk group, insurance status, and income. Accounting for existing PrEP payer mechanisms, we estimated annual uncovered costs for PrEP medication, clinical visits, and laboratory testing based on the 2021 PrEP clinical practice guideline. Of 1.2 million US adults with PrEP indications in 2018, we estimated that 49,860 (4 percent) of them had PrEP-related uncovered costs, including 32,350 men who have sex with men, 7,600 heterosexual women, 5,070 heterosexual men, and 4,840 people who inject drugs. Of those 49,860 people with uncovered costs, 3,160 (6 percent) incurred $18.9 million in uncovered costs for PrEP medication, clinical visits, and lab testing, and 46,700 (94 percent) incurred $83.5 million in uncovered costs for only clinical visits and lab testing. The total annual uncovered costs for adults with PrEP indications were $102.4 million in 2018. The proportion of people with uncovered costs for PrEP is less than 5 percent among adults with PrEP indications, but the magnitude of costs is significant.