With the growing recognition of the critical role that risk communication plays in a public health emergency, a number of articles have provided prescriptive best practices to enhance such communication. However, little empirical research has examined perceptions of the quality of communication, the impact of uncertainty on changing communication, use of information sources, and trust in specific government spokespersons. Similarly, although there is significant conceptual focus on trust and communication as important in vaccination intent and acceptance, little research has explored these relationships empirically. We conducted an online survey in late January 2010 with a nationally representative sample (N = 2,079) that included Hispanic and African American oversamples. The completion rate was 56%. We found that public health officials were the most trusted spokespersons, with President Obama being the most highly trusted elected official. Demographic variables, including race, accounted for 21% of the variance in trust of the president. Perceptions of the quality of communication were high, including significant understanding of uncertainty and appreciation for officials' openness about evolving information. Other factors that contributed to vaccination acceptance were quality of communication, closely following the news, and confidence in the vaccine because of a role model effect of the Obama daughters' immunizations; these factors significantly increased trust in government actions. Because the challenges of communication often vary over the course of a pandemic, there is a consistent need to pay close attention to both communication content and delivery and prepare public health officials at all levels to be effective communicators.