A growing number of patients undergoing total knee arthroplasty (TKA) is at working age and need to return to work (RTW) after surgery. The aim of this systematic review is to give an overview of the literature regarding RTW after TKA and beneficial and limiting factors influencing this process. A systematic search in four electronic databases was conducted in November 2019 to identify studies describing RTW after primary TKA in patients aged 65 years or younger. Study characteristics and data on work status before and after surgery were extracted. All studies were assessed for risk of bias. Fourteen studies published between 2009 and 2019 were included in this review, accounting for a total of 3,073 patients. The percentage of patients working after TKA ranged from 36 to 89%, and the fraction of patients working before and returning to work after surgery ranged from 40 to 98%. Mean time of RTW ranged from 7.7 to 16.6 weeks. Most important factors associated with a slower or no RTW were a more physical nature of employment and preoperative absence from work. The majority of patients undergoing TKA returned to work postoperatively. However, comparison between studies is seriously hampered by the wide variation regarding the definition and timeframe used to measure the work status. Therefore, standardized outcome measures for studies investigating RTW after TKA are warranted. We identify this review as level-I evidence (systematic review of level-I and level-II studies).