To evaluate the utility of home spirometry (HS) versus office spirometry (OS) in assessing treatment response to azithromycin in bronchiolitis obliterans syndrome (BOS). 239 Lung transplant recipients were retrospectively studied. ΔFEV1±10% from FEV1 at azithromycin initiation for ≥7 consecutive days in HS or ≥2 measures in OS were taken as cut-off for response or progression. Based upon HS, 161/239 (67%) patients were progressive despite macrolide, 19 of who exhibited transient improvement in FEV1 (11%). Time to progression was 29 (13-96) days earlier with HS than in OS. Forty-six (19%) recipients responded in HS after median 81 (22-343) days, whilst 22% remained stable. Concordance in azithromycin treatment response between OS and HS was observed in 210 of 239 patients (88%). Response or stabilization conferred significant improvement in survival (p=0.005). Transient azithromycin responders demonstrated improved survival when compared to azithromycin refractory patients (p=0.034). HS identified azithromycin refractory patients significantly earlier than OS, possibly facilitating aggressive treatment escalation that may improve long-term outcome. Treatment response to azithromycin should be assessed 4 weeks after initiation. Responders demonstrated best survival, with even transient response conferring benefit. Macrolide-refractory BOS carried the worst prognosis.