This retrospective study examines the effect of guidelines on clinical decision-making in the treatment of acute infections in nursing home residents. Among 110 patients followed over 7 years, infections caused 54% of acute medically attended problems, 48% of hospitalizations, and 63% of deaths. Patients designated to receive comfort care, when compared with maximum care patients, had a higher percentage of acute problems, hospitalizations, and deaths caused by infections. Antibiotic treatment was given far less often to comfort care patients with respiratory, urinary tract, and skin infections. Implications of such an intervention in nursing home care are discussed.