The study aims to systematically extract and analyse data about Quality of Life (QoL) in the transgender population. A systematic literature search and meta-analysis were conducted using the MEDLINE, EMBASE, PubMed, and PsycINFO databases, up to July 2017. Only English language quantitative studies, in adults, which reported the means for validated QoL measures were included. Random-effect meta-analysis was adopted to pool data and estimate the 95% Confidence Intervals (CI). From 94 potentially relevant articles, 29 studies were included within the review and data extraction for meta-analysis was available in 14 studies. The majority of the studies were cross-sectional, lacked controls and displayed moderate risk of bias. Findings from the systematic review suggested that transgender people display poor QoL, independent of the domain investigated. Pooling across studies showed that transgender people report poorer mental health QoL compared to the general population (−0.78, 95% CI = −1.08 to −0.48, 14 studies). However, meta-analysis in a subgroup of studies looking at QoL in participants who were exclusively post-CHT found no difference in mental health QoL between groups (−0.42, 95% CI = −1.15 to 0.31; 7 studies). There was insufficient data for a pre-treatment subgroup. Evidence suggests that transgender people have lower QoL than the general population. Some evidence suggests that QoL improves post-treatment. Better quality studies that include clearly defined transgender populations, divided by stage of gender affirming treatment and with appropriate matched control groups are needed to draw firmer conclusions.