This study explores individual and contextual risk factors for the onset of work interfering with private life (WIL) and private life interfering with work (LIW) among self-employed men and women across European countries. It also studies the relationship between interference (LIW and WIL) and wellbeing among self-employed men and women and the effect of macro level risk factors. Data from the fifth round of European Working Conditions Survey was utilized and a sample of self-employed men and women with active businesses was extracted. Applying multilevel regressions, results show that though business characteristics are important for level of WIL, time demand is the most evident risk factor for WIL and LIW. There is a relationship between wellbeing and WIL and LIW respectively, and time demands is the most important factor in this relationship. Gender equality on the labor market did not relate to level of interference, nor did it mediate the relationship between interference and wellbeing. However, the main and most important risk factor for experiencing WIL and LIW and for how interference relate to wellbeing is gender relation processes in work and life, both on individual and contextual level.