The aim of this study was to evaluate the effect of problem-based learning (PBL) on university students' satisfaction with and academic performance in a course on epidemiology and social and demographic health. The participants in this interventional study were 529 students (272 in the intervention group and 257 in the control group) enrolled in a medical degree programme during the academic years 2010-2011 and 2011-2012 in Spain. The intervention consisted of the use of a list of problems designed for small-group study in one of the practical sessions (Interpretation of Epidemiological Parameters). We compared students' satisfaction and performance after either PBL or conventional teaching methods. Students' satisfaction and academic performance were significantly better in the PBL group than in the traditional-learning group. Satisfaction with teaching was the main predictor of academic performance. After adjustment for level of satisfaction, the difference between groups in academic performance disappeared.