Pensacola Simulator Sickness Questionnaire (SSQ) is a valuable method to analyse symptoms evoked by exposure to a flight simulator environment that can also be adopted to evaluate the effectiveness of preventive tools, aiming at reducing simulator sickness (SS). In this study we analysed SSQ data in subjects undergoing a standard ground based spatial disorientation training inside a flight simulator, in order to evaluate the SS prevention obtained with two different pharmacological tools. Twelve males volunteers participated to an experimental design based on a double-blind, balanced administration of either 30 mg cinnarizine (CIN), or Cocculus Indicus 6CH (COC), or placebo (PLC) before one trial of about one hour spent inside a spatial disorientation trainer. All subjects underwent the three different conditions (CIN, COC, PLC) during 3 non-consecutive days separated by at least 2 weeks. During each experimental day, all subjects filled in SSQ. In addition, both postural instability (with the use of a static stabilometric platform), and sleepiness symptoms were evaluated. All the tests were performed before and after the simulated flight, at different times, in one-and-half-hour intervals. Results indicated a strong increase of sickness after flight simulation that linearly decreased, showing pre-simulator scores after 1.30 hours. In contrast to both PLC and COC, CIN showed significant side effects immediately following flight simulation, with no benefit at the simultaneous SSQ scores. Globally, no highly significant differences between COC and PLC were observed, although a minor degree of postural instability could be detected after COC administration. As far as the present exposure to a simulator environment is concerned, none of the pharmacological tools administered in this study resulted effective in reducing SS symptoms as detected by the SSQ. Moreover, CIN significantly increased sleepiness and postural instability in most subjects.