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Objectives: To evaluate the use of diagnostic testing before treating an infection in nursing home (NH) residents suspected of having a urinary tract infection (UTI) or pneumonia., Design: Prospective longitudinal study nested within a randomized trial, using data from control sites., Setting: Six NHs in southeast Michigan., Participants: NH residents with an indwelling urinary catheter, enteral feeding tube, or both (N = 162) with 695 follow-up visits (189 (28%) visits with an infection)., Measurements: Clinical and demographic data-including information on incident infections, antibiotic use, and results of diagnostic tests-were obtained at study enrollment, after 14 days, and monthly thereafter for up to 1 year., Results: One hundred (62%) NH residents had an incident infection requiring antibiotics, with substantial variations between NHs. In addition to presence of infection-specific symptoms, change in function was a significant predictor of ordering a chest X-ray to detect pneumonia (odds ratio (OR) = 1.7, P = .01). Similarly, change in mentation was a significant predictor of ordering a urinalysis (OR = 1.9, P = .02), chest X-ray (OR = 3.3, P < .001), and blood culture (OR = 2.3, P = .02). Antibiotics were used empirically, before laboratory results were available, in 50 of 233 suspected cases of UTI (21.5%) and 16 of 53 (30.2%) suspected cases of pneumonia. Antibiotics were used in 17% of visits without documented clinical or laboratory evidence of infection., Conclusion: Constitutional symptoms such as change in function and mentation commonly lead to diagnostic testing and subsequent antibiotic prescribing. Antibiotic use often continues despite negative test results and should be a target for future interventions., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)