OBJECTIVES: To compare long-term health-related quality of life (HRQL) in single and bilateral lung transplant recipients independent of the underlying disease, and in a subset of patients with native pulmonary emphysema. METHODS: Forty-four lung transplant recipients (mean [+/- SD] age, 44.8 +/- 11.6 years) were followed up for > 2 years after single lung transplantation (LTx) [14 recipients] or bilateral LTx (30 recipients). Data were prospectively collected, before undergoing LTx and annually after undergoing LTx, measuring FEV1, 6-min walk test (6MWT) results, and quality of life using the St. George respiratory questionnaire (SGRQ) and a visual analog scale (VAS). The SGRQ addresses three domains, namely, respiratory symptoms, accomplishment of routine activities, and disease impact on daily life. RESULTS: Statistically significant correlation coefficients were found comparing the SGRQ and the VAS (r = 0.812; p < 0.0001), the SGRQ and the 6MWT (r = 0.610; p < 0.0001), and the SGRQ and the FEV1 (r = 0.523; p < 0.0001) in all patients. Significant improvements on the FEV1, 6MWT, and SGRQ were observed after LTx in both single and bilateral LTx recipients. Increased risk for the development of bronchiolitis obliterans syndrome (BOS) [relative risk, 2.86; 95% confidence interval, 1.22 to 6.67; p = 0.03] and significantly lower FEV1 values were observed in patients following a single graft, compared to that in patients following a bilateral graft (p < 0.01). In contrast, the 6MWT and the SGRQ scores were not significantly different between recipients of single and double LTx. The same patterns of results were observed in comparisons between single and bilateral lung recipients with prior pulmonary emphysema. CONCLUSIONS: Despite poorer FEV1 recovery and increased risk of BOS after LTx, single lung transplant recipients had comparable long-term exercise tolerance and quality-of-life scores as patients who received bilateral transplants. These results suggest the limited influence of functional performance on objective and subjective markers of HRQL recovery after LTx.