Introduction: The fixed dose combinations used in chronic obstructive pulmonary disease (COPD) patients need their rationale evaluation. If there is no added benefit; then it amounts economic burden on the society, reduced compliance, and unsuccessful therapy. This study evaluated the effectiveness of three regimens of dry powder inhaled preparations including tiotropium 18 μg once a day; tiotropium 18 μg plus formoterol 12 μg once a day, and tiotropium 18 μg once a day plus formoterol 12 μg twice a day in moderate COPD patients. Materials and Methods: A randomized, double‑blind, placebo‑controlled, active drug controlled parallel design study was conducted in 42 moderate COPD patients without any other comorbidity. Three (R1, R2, and R3) regimens were evaluated in patients to assess the appropriate evidence‑based pharmacotherapy regimen. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), Borg’s scale of dyspnea, and vital signs (blood pressure and pulse rate) were measured on serial time points for 24 h. Results: The trough FEV1 values of R1, R2, and R3 in liters were 1.836 ± 0.51, 1.886 ± 0.47, and 1.805 ± 0.37, respectively and did not show any statistical difference. No statistical significance was observed in FVC (liters), FEV1% predicted, ΔFEV1 (liters), ΔFEV1% predicted, ΔFVC % predicted, and Δ FVC (liters) except in 24 h FVC percentage predicted values where P ‑ value for R3 is in the range between 0.05 and 0.1 over R1. Conclusions: Study shows that tiotropium alone once a day is the evidence based and rationale pharmacotherapy in moderate COPD. There is no advantage or statistical significance of adding long acting β2 agonists (LABA) such as formoterol to tiotropium either for 12 h (once daily) or 24 h (twice daily).