Nocardia is an opportunistic pathogen in solid organ transplantation for which long-term sulfonamide therapy is considered the treatment of choice. We report a patient 7 months status post-orthotopic heart transplantation with Nocardia nova bacteremia and pneumonia. Initial treatment consisted of intravenous trimethoprim-sulfamethoxazole, which cleared blood cultures, but the patient subsequently went into renal failure and required alternative therapy. This report describes the first case of N nova bacteremia after orthotopic heart transplantation successfully treated with clarithromycin. All therapy should be guided by antibiotic sensitivity, and combination therapy should be considered in acutely ill patients and cases where in vitro synergy has been documented. This case suggests that clarithromycin can be an alternative treatment in cases of sulfonamide resistance, intolerance, or allergy.