Robot-Assisted Therapy (RT) is an innovative approach to neurological rehabilitation that uses intensive, repetitive, interactive, and individualized practice. This systematic review aimed to investigate the effectiveness of RT on the body function and structure of people with upper limb impairments (PROSPERO registration: CRD42017054982). A search strategy conducted on seven databases identified randomized controlled studies. Methodological quality was assessed using the PEDro scale. When possible, the data were pooled, the strength of evidence was assessed using the GRADE system, and the effect sizes were assessed using Cohen coefficient. Subgroup analyses investigated the impact on the estimated effects of the following parameters: methodological quality; portion of the assessed upper limb; duration of stroke; and intervention dose and duration. Thirty-eight studies involving 1174 participants were included. Pooled estimates revealed small effects of RT on motor control and medium effects on strength compared with other intervention (OI) at a short-term follow-up. Standardized differences in means were as follows: 0.3 (95% CI 0.1 to 0.4) and 0.5 (95% CI 0.2 to 0.8). Effects at other time points and on other investigated outcomes related to body function and structure were not found (p>0.05). The strength of the current evidence was usually low quality. Subgroup analyses suggested that the methodological quality, and duration and dose of RT may influence the estimated effects. In conclusion, RT has small effects on motor control and medium effects on strength in people with limited upper limb function. Poor methodological quality, and lower treatment dose and duration may impact negatively the estimated effects.