The goal of our study was to assess acute respiratory responses to using e-cigarettes in exclusive e-cigarette users (E-Group) and dual users (T/E-Group) and to compare these effects with responses to smoking tobacco-cigarettes in tobacco smokers (T-Group). The study included 120 adults (age: 21.7 ± 2.1 years) divided into 4 groups (n = 30 each): Controls, T-, E-, T/E-Group. Spirometric status, O2 saturation, exhaled FeNO levels, exhaled CO levels, and airway temperature were assessed before the use of an e-cigarette (E-, T/E-Group) or tobacco cigarette as well as 'minute 1' and 'minute 30' after smoking. Controls used an e-cigarette without e-liquid. Lower (p < 0.05) baseline values of FeNO were found in T-Group (15.4 ppb) and in T/E-Group (15.0 ppb) than in Controls (19.6 ppb). Following exposure, and compared with Controls, T-, and T/E-Group had a significant decrease (p < 0.05) in PEF and MEF75. Mean FeNO values decreased on 'minute 1' in T-Group (by 2.1 ppb), E-Group (by 1.5 ppb) and in T/E-Group (by 2.2 ppb). Other effects included increase in temperature of exhaled air (p < 0.05). The use of e-cigarettes is associated with decreased FeNO and airflow indices (PEF, MEF75), but an increase in airway temperature. These changes are similar to those after exposure to tobacco cigarette smoke.