Although there is no agreement on the optimal treatment of patients presenting with a first episode of primary spontaneous pneumothorax, the majority of physicians prefer chest tube drainage for air evacuation. Manual aspiration of air has been proposed by some, but lack of sound comparative data and safety data has limited its use. In this first randomized, prospective, multicenter pilot study, 60 patients with a first episode of primary spontaneous pneumothorax were randomly allocated to manual aspiration (n = 27) or chest tube drainage (n = 33). Immediate success was obtained in 16 out of 27 (59.3%) in the manual aspiration group, and in 21 out of 33 (63.6%) in the chest tube drainage group (p = 0.9). One-week success rates were 25 out of 27 (93%) in the intention-to-treat manual aspiration group and 28 out of 33 (85%) in the chest tube drainage group (p = 0.4). Fourteen of 27 manual aspiration patients (52%) were hospitalized, versus 100% of the chest tube drainage patients (p < 0.0001). Recurrence rates with at least 1-year follow-up were 7 out of 26 (26%) in the manual aspiration group, and 9 out of 33 (27.3%) in the chest tube drainage group (p = 0.9). There were no complications associated with manual aspiration. Although statistical power is insufficient to formally confirm therapeutic equality, this pilot study suggests that in first episodes of primary spontaneous pneumothorax, manual aspiration seems equally effective as chest tube drainage and is safe, well tolerated, and feasible as an outpatient procedure in the majority of patients.