The PARI-IS Study is a double-blind placebo-controlled randomized clinical trial to study the effect of an immunostimulating agent to prevent acute respiratory exacerbation in patients with COPD. Three hundred eighty-one ambulatory patients (190 placebo and 191 immunostimulant) were followed at home for 6 mo by experienced research nurses. The risk of having at least one episode of acute exacerbation (primary outcome) was similar in the two groups (p = 0.872). In contrast, the total number of days of hospitalization for a respiratory problem was 55% less in the group treated with OM-85 BV (287 d) than in the group treated with placebo (642 d). Patients treated with OM-85 BV spent an average of 1.5 d in hospital compared with 3.4 d for patients treated with placebo (p = 0.037). The risk of being hospitalized for a respiratory problem was 30% lower in the treated group (16.2%) than in the placebo group (23.2%); p = 0.089. Eight deaths were observed: two in patients treated with OM-85 BV and six in patients treated with placebo (p = 0.153). During the course of the study dyspnea improved slightly in patients treated with OM-85 BV, whereas it deteriorated slightly in patients receiving placebo (p = 0.028). These results suggest that this immunostimulating agent may be beneficial for patients with COPD by reducing the likelihood of severe respiratory events leading to hospitalization.