As medical management and surgical techniques continue to improve, patients with congenital heart disease are surviving further into adulthood and seeking to participate in multiple activities. Given the increasing popularity of adventure recreation, it is likely that many of these individuals will express interest in travel to and activities at high altitude. At first glance, the hypoxia associated with acute altitude exposure would appear to pose high risks for patients with underlying cardiopulmonary disease, but few studies have systematically addressed these concerns in the adult congenital heart disease population. In this review, we consider the safety of high-altitude travel in these patients. After reviewing the primary cardiopulmonary responses to acute hypoxia and the risks of high altitude in all individuals regardless of their underlying health status, we consider the risks in adult congenital heart disease patients, in particular. We focus on broad concerns that should be considered in all patients such as whether they have underlying pulmonary hypertension, the adequacy of their ventilatory responses, and their ability to compensate for hypoxemia and right-to-left shunting. We then conclude by providing basic recommendations for pretravel assessment in patients with congenital heart disease of moderate or great complexity.