Aspergillus, a saprophytic fungus ubiquitously present in the environment, is rarely pathogenic in immunocompetent hosts, as such invasive Aspergillus osteomyelitis in immunocompetent hosts is uncommonly reported. A 50-year-old immunocompetent man, intravenous drug user with hepatitis C and diabetes mellitus, presented with lumbago and was diagnosed with L5-S1 discitis/osteomyelitis with associated phlegmon, s1 nerve root impingement, and no epidural abscess in August 2014. Needle biopsy cultures were negative. The patient was readmitted in October 2014 with worsening lumbago after completion of antibiotics. Inflammatory markers were significantly elevated (erythrocyte sedimentation rate = 97 mm in 1 hour; C-Reactive Protein = 13.5 mg/dL) and magnetic resonance imaging demonstrated ongoing acute L5-S1 discitis/osteomyelitis with involvement of vertebral bodies and endplate erosion, progressive impingement of the s1 nerve root, and no epidural abscess. Intraoperative cultures and histopathology were consistent with invasive aspergillosis and was treated successfully with voriconazole. Lumbar vertebral osteomyelitis in immunocompetent patients is a potentially life-threatening diagnosis often made late in the presentation because of nonspecific serologic test options and difficulty culturing fungal organisms. Open biopsy should be obtained when suspicion for a nonbacterial pathogen is high, especially after failure of antibacterial therapy. Aspergillosis should be considered in patients with a history of intravenous drug use, because drugs can be contaminated with Aspergillus. Voriconazole is the antifungal of choice for invasive aspergillosis osteomyelitis with excellent oral bioavailability, bone penetrance, and superior adverse effect profile compared with amphotericin B. Treatment for invasive aspergillosis osteomyelitis should involve both surgical and medical interventions.