OBJECTIVES: The UPLIFT trial demonstrated in 5,993 patients with moderate to very-severe chronic obstructive pulmonary disease (COPD) that 4 years of tiotropium bromide were associated with improvements in lung function, quality of life, and exacerbations compared with placebo. The aim of this study is the economic assessment of tiotropium when included in COPD routine care (RC) for specific groups of Italian COPD patients. METHODS: A probabilistic patient-level simulation Markov model was developed over a lifetime horizon, with one-year cycles and a 3.5% annual discount rate. Patients were characterized by gender, age, height, smoking status and FEV1. FEV1 time trend was modelled based on the decline recorded in UPLIFT. The mortality of the general Italian population adjusted by smoking status and FEV1 was adopted. Health utilities derived from published Italian studies, while their variation from the UPLIFT. Exacerbation rates derived from an Italian observational prospective study and were adjusted for the relative risk (RR) reported in UPLIFT. Direct sanitary costs were considered. Healthcare resource consumption for RC, exacerbations and SAEs derived from Italian observational studies and were valued according to current price and tariffs. Cost-effectiveness was assessed for the overall cohort and for subgroups of patients by age, sex, GOLD stage and smoking attitude. RESULTS: In the whole cohort, patients treated with tiotropium gained an average (95%CI) 0.50 (-1.63 – 6.27) LYs and 0.42 (-0.25 – 3.05) QALYs with respect to RC. The incremental lifetime cost was €3,357 (- €10,669 – €29,820). The incremental cost-effectiveness ratio (ICER) was €7,916 /QALY. In the subgroups analysis the ICER ranged from a minimum of €6,627/QALY (females, GOLD III) to a maximum of  €13,187/QALY (age <65y, GOLD IV). CONCLUSIONS: The inclusion of tiotropium in RC for moderate to very severe COPD patients represents good value for money in Italy. The analysis across subgroups demonstrated a good stability of the model.