Simultaneous left flank pain and fever are often initially attributed to urinary tract infections or pyonephritis. This case is on a 47-year-old man who was first diagnosed with acute pyelonephritis due to having left back pain and fever for 2 days. However, after renal infarction was found through kidney computed tomography (CT), he was then carefully assessed and found to have heart murmur, finger nodules (Osler's node), and a history of heroin addiction. Infective endocarditis was then considered and confirmed by echocardiogram. After receiving Oxacillin sodium treatment, the patient's condition improved. Therefore, if the clinical symptoms of pyonephritis do not improve after antibiotic therapy, further image study is necessary to rule out other possibilities. If the image study shows renal infarction, we should carefully assess whether the patient has heart murmur, skin lesions, or drug addiction history. If so, infective endocarditis should be highly suspected.