Background: In recent years, Canadian health care professionals have observed an increase in vaccine refusal. The objective of this study is to review published literature and identify the main themes related to vaccine hesitancy and barriers to vaccination in Canadian adults and recent immigrants. Methods: A qualitative systematic review was performed. A comprehensive search of MEDLINE (1946 to January 2021) and EMBASE (1974 to January 2021) was conducted to identify existing literature that addressed the primary research question. Studies were eligible for inclusion if the study population involved 1) the general population, 2) Indigenous populations, 3) recent immigrants to Canada or 4) Canadian health care professionals. Results: Thirty-four studies were included with a focus on the general population ( n = 22), health care professionals ( n = 10) and recent immigrant populations ( n = 2). The most frequently reported barriers were lack of vaccine information (41%), lack of access to vaccination (38%), fear of adverse reactions (38%), financial reasons (29%), lack of awareness of vaccine existence (29%), antivaccine sentiments (24%), notion that older adults do not need vaccination (18%), misconceptions on vaccine effectiveness (12%), potential sexual health promotion stigma (6%) and fear of needles (3%). Interpretation: Barriers to vaccination among Canadians and recent immigrants continue to be a challenge in the health care system. Conclusions: The greatest yield in improving vaccination rates is likely to come from supporting vaccine-hesitant individuals in shifting their thinking to greater vaccine acceptance. Pharmacists are well positioned to address vaccine hesitancy and involvement through education, facilitation and administration of vaccines. Can Pharm J (Ott) 2022;155:xx-xx.