Sex is a strong prognostic factor in stage IV non-small-cell lung cancer patients and should be considered in survival rate estimation.

•Sex is a major factor in disease, but it is seldom taken into account for survival estimations.•Using RWD we confirm that NSCLC females had a significantly better prognosis than NSCLC males.•The effect size of sex on survival is high supporting sex-based medicine as a new paradigm in medical practice.