This study determines whether COVID-related risk-taking behavior was different among Republicans, Democrats, and Independents, in adults with elevated chance of severe complications from COVID–19. Using US national survey data collected September 30–October 27, 2020 (N = 6095), behaviors in the prior week examined were: 7 potentially risky activities, mask wearing anywhere, and mask wearing while undertaking each activity. Differences among political affiliations were estimated for adults with 0 and with ≥1 medical risk factors for severe complications, adjusting for sociodemographic factors. Among adults with medical risk factors, the adjusted number of potentially risky activities was higher among Republicans (3.83) but not Independents (3.17) relative to Democrats (2.98). The adjusted percentage of adults with medical risk factors who wore a mask anywhere in the past week was lower for Republicans (87%) and Independents (91%) than for Democrats (97%). While undertaking each specific activity, the adjusted percentage of at-risk adults never wearing a mask was higher for Republicans than Democrats: 24% vs 8% at bar/club; 6% vs 0% at grocery/pharmacy; 63% vs 30% visiting at friend's home; 68% vs 41% hosting visitors; 30% vs 5% at gathering of ≥10 people; 25% vs 11% while within 6 ft of someone they do not live with. Rates of mask wearing among political Independents were between rates among Democrats and Republicans. Efforts to reduce COVID-related risky behavior should recognize that although Republicans take more risks, rates of mask wearing at common activities are low across political affiliations, even for populations vulnerable to severe complications.