The use of head-mounted displays (HMD) for virtual reality (VR) application-based purposes including therapy, rehabilitation, and training is increasing. Despite advancements in VR technologies, many users still experience sickness symptoms. VR sickness may be influenced by technological differences within HMDs such as resolution and refresh rate, however VR content also plays a significant role. The primary objective of this systematic review and meta-analysis was to examine the literature on HMD’s that report Simulator Sickness Questionnaire (SSQ) scores to determine the impact of content. User factors associated with VR sickness were also examined. A systematic search was conducted according to PRISMA guidelines. Fifty-five articles met inclusion criteria, representing 3,016 participants (mean age range 19.5-80; 41% female). Findings show gaming content recorded the highest total SSQ mean 34.26 (95%CI 29.57-38.95). VR sickness profiles were also influenced by visual stimulation, locomotion and exposure times. Older samples (mean age ≥35 years) scored significantly lower total SSQ means than younger samples, however these findings are based on a small evidence base as a limited number of studies included older users. No sex differences were found. Across all types of content, the pooled total SSQ mean was relatively high 28.00 (95%CI 24.66-31.35) compared with recommended SSQ cut-off scores. These findings are of relevance for informing future research and the application of VR in different contexts.