The authors carried out the study reported here to assess which variables are most predictive of the risk of medical students' experiencing academic difficulties and to assess when these students are most susceptible to encountering those difficulties. The entering class of 1992 was chosen as the study population because it was the first matriculating class in which the majority of students (88%) applied to medical school with scores from the revised Medical College Admission Test (MCAT), first implemented in 1991. The primary event of interest in this study was the first occurrence of one of the following events because of academic difficulty: withdrawal, leave of absence, dismissal, or delay of graduation date. The variables examined were MCAT scores undergraduate science GPA, undergraduate institutional selectivity, undergraduate major, racial-ethnic background, sex, and age upon entering medical school. Survival analysis was used to assess which variables were most predictive of the risk of academic difficulty and when students with different characteristics were most at risk. The results of the survival analysis indicated that (1) while the risk and timing of academic difficulty varied across the groups studied, a majority of the students who experienced academic difficulty eventually graduated from medical school and (2) students with non-science undergraduate majors did not have a greater risk of academic difficulty. The results confirm previous findings that increased risk of academic difficulty is associated with low MCAT scores, low science GPA, low undergraduate institutional selectivity, being a woman, being a member of a racial-ethnic underrepresented minority, or being older. The study findings can be generalized to help in early identification of students who are more likely to be at risk of experiencing academic difficulty. Knowing when these students are more likely to be at risk can help medical schools develop targeted remedial and enrichment programs. Further studies are needed to investigate school-related factors associated with risk.