Objective: To test the feasibility of and interactions among three software-driven critical care protocols. Design: Prospective cohort study. Setting: Intensive care units in six European and American university hospitals. Patients: 174 cardiac surgery and 41 septic patients. Interventions: Application of software-driven protocols for cardiovascular management, sedation, and weaning during the first 7days of intensive care. Measurements and results: All protocols were used simultaneously in 85% of the cardiac surgery and 44% of the septic patients, and any one of the protocols was used for 73 and 44% of study duration, respectively. Protocol use was discontinued in 12% of patients by the treating clinician and in 6% for technical/administrative reasons. The number of protocol steps per unit of time was similar in the two diagnostic groups (n.s. for all protocols). Initial hemodynamic stability (a protocol target) was achieved in 26 ± 18 min (mean ± SD) in cardiac surgery and in 24 ± 18 min in septic patients. Sedation targets were reached in 2.4 ± 0.2 h in cardiac surgery and in 3.6 ± 0.2 h in septic patients. Weaning protocol was started in 164 (94%; 154 extubated) cardiac surgery and in 25 (60%; 9 extubated) septic patients. The median (interquartile range) time from starting weaning to extubation (a protocol target) was 89 min (range 44-154 min) for the cardiac surgery patients and 96 min (range 56-205 min) for the septic patients. Conclusions: Multiple software-driven treatment protocols can be simultaneously applied with high acceptance and rapid achievement of primary treatment goals. Time to reach these primary goals may provide aperformance indicato