The postdoc appointments taken by many new doctorate recipients in the biological, health, physical, and mathematical sciences represent a significant public and private investment in these scientists' training. Dissatisfaction with postdoc appointments may deter some of the most talented scientists from continuing research careers. Dissatisfied postdocs are a concern for universities and other organizations because they rely on postdocs' research productivity and have realized the need to incorporate postdocs more fully into the community of scholars. Individual scientists also have a strong interest in avoiding unsatisfactory choices at the critical juncture in their early careers where they select a postdoc appointment. This paper draws on survey data from 764 postdocs at major US universities to examine the factors associated with dissatisfaction. Results of an ordered probit regression indicate that the type of research conducted, its connection to career goals, supervision, and demographic characteristics affect the probability that a postdoc will be dissatisfied. The paper also analyzes the mediating roles of autonomy, advisor interaction, and advisor involvement in commercialization activities on the relationship between program quality and dissatisfaction. The paper concludes with implications for public and institutional policy and for early career scientists considering postdoc appointments.