Introduction Hypokalaemia is an unrecognised complication of vancomycin therapy. Case presentation We present a 68-year-old female with an infected hindquarter amputation site who had incurred severe hypokalaemia with recurrent episodes of cardiac arrest requiring cardioversion shortly after commencing intravenous vancomycin therapy. The cause of hypokalaemic cardiac arrest was thought to be due to administration of low dose furosemide, however, holding potassium-wasting diuretics did not restore normal serum potassium concentrations. After an extended period of conservative management with potassium supplementation, spironolactone therapy and cautious serum electrolyte monitoring, cessation of vancomycin led to the complete resolution of hypokalaemia. Conclusion Clinicians should be aware that vancomycin therapy, even in the presence of normal renal function, may be a reversible cause of severe hypokalaemia.