Background <p>Among gastrointestinal stromal tumors patients, many authors have reported longer overall survival for female sex regardless of stage. Other studies showed more favourable prognosis for young women, while others found no effect of sex on outcome. Few data about survival differences by sex are available on patients with unresectable/metastatic gastrointestinal stromal tumors (mGIST) receiving imatinib. The study aims to perform a trial-level analysis of metastatic gastrointestinal stromal tumors patients treated with imatinib to define the effect of sex on overall survival.</p> Methods <p>After a systematic literature review, studies enrolling mGIST patients receiving upfront imatinib and reporting hazard ratios and confidence intervals of the relationship of sex with overall survival (OS) were selected. A meta-analysis was performed, calculating a global effect size. Finally, the study explored the effect on the relationship of other baseline variables, such as age, sex, tumor location, and patient origin.</p> Results <p>Fifteen articles were selected, including 3612 patients. The meta-analysis documented longer OS among women, with significant overall effect size (HR 0.77, CI 0.71-0.84). Furthermore, there was no significant heterogeneity among studies (Q=9.13, <i>p</i>-value=0.8229; <i>I</i>^<i>2</i>=0%), while the effect of the relationship was not confirmed for tumors originating in the stomach.</p> Conclusions <p>The analysis documented better prognosis for female sex after upfront imatinib. The absence of heterogeneity between studies suggests that sex may condition a different response to imatinib. However, other factors, such as second malignancies and mutation patterns, may also contribute to the observed differences.</p>