Background: Opportunities for learning from real patients have decreased. Self-directed learning at times suitable for shift patterns are increasingly likely to become important. This study reports on the design and evaluation of game-based learning activities for virtual respiratory patients in Second Life. Methods: A virtual teaching hospital was created in Second Life (http://www.elearningimperial.com/index.php?option = com_content&task = view&id = 37&Itemid = 58). A respiratory ward has been designed with a pneumothorax patient focussing upon game-based learning activities (requesting investigations and planning management). Similar material was available as part of a respiratory emergencies e-learning module embedded in the year 3 medical undergraduate curriculum. Initial data about gaming competence was obtained from 118 full-time undergraduate medical students (mean age 22 years) who volunteered for the study. A stratified sample of 50 students was selected according to gender and high and low gamer categories and was randomly assigned into two groups. One group (23/25 attended) was given access to the game-based learning activities in Second Life and the second group (19/25 attended) was given access to the same content delivered as an interactive e-module. After use of the modules students in both groups completed a questionnaire involving 21 statements related to affective components, perceived control, perceived usefulness and behavioural components (scored on a 5-point Likert scale). 2 or Fisher's exact test was used to compare categorical variables between both groups. The questions were combined into groups 1-3 (disagree) and 4-5 (agree). Results: There was no evidence of a difference in general attitude for Second Life (p = 0.66) or the e-module (p = 0.86) between gender. There was some evidence of an association between gaming competence and gender for Second Life (p = 0.03) or e-module (p = 1.00). Conclusions: The results suggest some evidence of an association between previous gaming experience and gender in favour of Second Life, but the pilot study shows that significant previous experience of Second Life is necessary for this learning activity. The current technology limits the number of learners that can attend the virtual patient in the same way as physical space limits the number around a bed in an existing hospital ward.