Background Few studies have investigated the incidence and management of adverse drug reactions that occur during home parenteral therapy. Aim To determine the incidence, characteristics and risk factors for adverse drug reactions associated with home parenteral therapy; to evaluate the management of these reactions; and to determine the ideal contents of an anaphylaxis kit. Method 673 consecutive patients starting home parenteral therapy were recruited from the Sydney West Area Health Service (June 2002 to November 2004). Data were collected on patient characteristics; diagnosis; known drug allergies; concurrent medications; drug dose and frequency; duration of treatment; and adverse drug reactions, their management and outcomes. Results 714 treatment courses were administered to 673 patients. Commonly treated conditions were cellulitis (313 courses; 44%), orthopaedic infections (73 courses; 10%) and wound infections (63 courses; 8.8%). Frequently prescribed drugs were cephazolin (376 courses; 50%), ceftriaxone (149 courses; 20%) and vancomycin (52 courses; 7.1%). Adverse drug reactions occurred in 38 (5.3%) courses, of which 5 were ranked as serious or life‐threatening. Adverse drug reactions included skin reactions in 18 (2.5%) courses, abdominal symptoms in 8 (1.1%) courses, and vascular symptoms in 5 (0.7%) courses. Risk factors included concurrent beta‐blocker use, which was associated with an adverse drug reaction in 9 out of 54 courses (OR 4.4; 95%CI 1.9–9.7; p = 0.0003). Conclusion There was a low incidence of adverse drug reactions with home parenteral therapy, with a small risk of serious reactions. Patients taking concurrent beta‐blockers may be at greater risk of adverse drug reactions when treated with parenteral drugs. Patients need to be screened for documented allergies, regularly monitored, and an anaphylaxis kit containing adrenaline and glucagon made available.