To prospectively develop and validate a predictive model for delirium based on precipitating factors during hospitalization, and to examine the interrelationship of precipitating factors and baseline vulnerability. Two prospective cohort studies, in tandem. General medical wards, university teaching hospital. For the development cohort, 196 patients aged 70 years and older with no delirium at baseline, and for the validation cohort, 312 comparable patients. New-onset delirium by hospital day 9, defined by the Confusion Assessment Method diagnostic criteria. Delirium developed in 35 patients (18%) in the development cohort. Five independent precipitating factors for delirium were identified; use of physical restraints (adjusted relative risk [RR], 4.4; 95% confidence interval [CI], 2.5 to 7.9), malnutrition (RR, 4.0; 95% CI, 2.2 to 7.4), more than three medications added (RR, 2.9; 95% CI, 1.6 to 5.4), use of bladder catheter (RR, 2.4; 95% CI, 1.2 to 4.7), and any iatrogenic event (RR, 1.9; 95% CI, 1.1 to 3.2). Each precipitating factor preceded the onset of delirium by more than 24 hours. A risk stratification system was developed by adding 1 point for each factor present. Rates of delirium for low-risk (0 points), intermediate-risk (1 to 2 points), and high-risk groups (> or equal to 3 points) were 3%, 20%, and 59%, respectively (P < .001). The corresponding rates in the validation cohort, in which 47 patients (15%) developed delirium, were 4%, 20%, and 35%, respectively (P < .001). When precipitating and baseline factors were analyzed in cross-stratified format, delirium rates increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline and precipitating factors were documented to be independent and statistically significant. A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium. Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive, and cumulative ways.