In the next few years, the number of long-term space missions will significantly increase. Providing safe concepts for emergencies including airway management will be a highly challenging task. The aim of the present trial is to compare different airway management devices in simulated microgravity using a free-floating underwater scenario. Five different devices for airway management [laryngeal mask (LM), laryngeal tube (LT), I-GEL, direct laryngoscopy (DL), and video laryngoscopy (VL)] were compared by n = 20 paramedics holding a diving certificate in a randomized cross-over setting both under free-floating conditions in a submerged setting (pool, microgravity) and on ground (normogravity). The primary endpoint was the successful placement of the airway device. The secondary endpoints were the number of attempts and the time to ventilation. A total of 20 paramedics (3 female, 17 male) participated in this study. Success rate was highest for LM and LT and was 100% both during simulated microgravity and normogravity followed by the I-GEL (90% during microgravity and 95% during normogravity). However, the success rate was less for both DL (60% vs. 95%) and VL (20% vs. 60%). Fastest ventilation was performed with the LT both in normogravity (13.7 ± 5.3 s; n = 20) and microgravity (19.5 ± 6.1 s; n = 20). For the comparison of normogravity and microgravity, time to ventilation was shorter for all devices on the ground (normogravity) as compared underwater (microgravity). In the present study, airway management with supraglottic airways and laryngoscopy was shown to be feasible. Concerning the success rate and time to ventilation, the optimum were supraglottic airways (LT, LM, I-GEL) as their placement was faster and associated with a higher success rate. For future space missions, the use of supraglottic airways for airway management seems to be more promising as compared to tracheal intubation by DL or VL.