Introduction Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is effective in treatment of major depressive disorder (MDD). The prevalence of depression is higher in women than in men. It has been observed that women respond better to selective serotonin reuptake inhibitors (SSRIs) than men, but not all studies confirm these findings, so it is difficult to generalize gender differences in pharmacotherapeutic antidepressant effect. A probable association of short-term antidepressant properties of rTMS with gender has been observed. Meta-analysis published in 2019. showed that rTMS MDD studies with higher proportion of women participants observed a higher response rates at 3rd and 6th months, but since the gender-related effects were not specifically analyzed it was not possible to draw conclusive conclusions. Men respond more strongly to placebo treatment but the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD is not associated with gender. Objective To investigate gender differences in the efficacy of 8-coil rTMS on major depressive disorder (MDD). Methods We performed an industry-independent, unicentric, randomized, controlled, single-blinded study from May 2020 to October 2020 in Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia. Patients were randomized into two groups: one treated with 8-coil rTMS and standard pharmacotherapy (47 patients) and the other treated with the standard pharmacotherapy alone (43 patients). We used a stratified (for age, gender and depression severity), permuted blocks randomization with the randomized block sizes of 4, 6 and 8 participants. The primary outcome was Hamilton Depression Rating Scale-17 (HDRS). Variables whose possible confounding effect we controlled by multivariable statistical analysis were: age, diagnosis, duration of illness, treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other antidepressants. Results After the adjustment for all preplanned possible confounding variables, the lowering of HAMD17 score after 4-weeks treatment was statistically significantly different between patients treated with 8-coil rTMS + standard pharmacotherapy, and patients treated with standard pharmacotherapy alone. In women, the lowering of HAM-D17 score over four weeks of treatment was statistically significantly and clinically relevantly larger in the experimental group treated with rTMS and standard pharmacotherapy than in the control group treated with standard pharmacotherapy alone (F (1, 26) = 7.49; p = 0.011; ω2 = 0.08; false discovery rate; FDR <10%). This could not be reliably claimed for men. The interaction of the study group, i.e. treatment with rTMS and standard pharmacotherapy or standard pharmacotherapy alone, and gender on the change in HAM-D17 scores from enrolment to after four weeks of treatment was not statistically significant after adjustment for age, age at MDD onset, diagnosis, treatment with SSRIs, SNRIs and other antidepressants (F (1, 74) = 2.05; p = 0.157; ω2 = 0.14). Conclusion It cannot be reasonably reliably claimed that there are differences in the effect of rTMS between men and women using the 8-coil, but the results indicate the need for further research.