Objective To identify potential predictors of undergraduate students who struggle during their medical training. Design Case-control study. Cases were students who had experienced academic or personal difficulties that affected their progression on the course ("strugglers"). Controls were selected at random from the corresponding year cohorts, using a ratio of four controls for each struggler. Setting University of Nottingham Medical School. Participants Students who entered the course over five consecutive years. Main outcome measures Likelihood ratios for independent risk factors for struggling on the course Results 10-15% of each year's student intake were identified as strugglers. Significant independent predictors of students being in this category were negative comments in the academic reference (likelihood ratio 2.25, 95% confidence intervals 1.44 to 3.50), lower mean examination grade at A level (2.19, 1.37 to 3.51), and the late offer of a place (1.98, 1.19 to 3.30). Male sex was a less significant risk factor (1.70, 1.09 to 2.65) as was a lower grade at GCSE science (2.13, 1.12 to 4.05). In UK students whose ethnicity was known, not being white was a significant predictor of struggling (2.77, 1.52 to 5.05) but the presence of negative comments was not. Age at entry to the course and the possession of a previous degree were not predictive. Conclusions Our results support retention of existing selection practices relating to academic achievement and critical review of students' references. We plan to undertake further investigation of the reasons why some students, including men, those with late offers and those from ethnic minority backgrounds, may do less well on the Nottingham course.