Purpose To examine the association and potential mediating factors between erectile dysfunction (ED) and mental health in generally healthy elderly men. Methods Data on sexual life and mental health were collected among 3,810 participants of the European randomized study on for prostate cancer (ERSPC). Response was 81%, average age 67 (range 57-78) years. ED was defined as (almost) always having problems in achieving or maintaining an erection if desired, or not being sexually active because of erectile problems. The SF-36 scale MH5 was used to assess mental health. The minimal clinical important difference (MCID) operationalized as a difference of at least half a standard deviation (SD), was used to indicate the relevance of differences in scores. We analyzed (ANCOVA) whether the importance of and satisfaction with sexual life were potential mediators between ED and mental health, after adjustment for age and use of erectile aids. Results Prevalence of ED was 19% (n=683). ED was significantly and negatively related to mental health (p<0.001). The mean mental health score was 88 (SD 11) in men who were very satisfied with their sexual life vs. 73 (SD 17) in very dissatisfied men, a difference exceeding the MCID. In univariate analyses, ED and ‘dissatisfaction with sexual life' were both associated with poor mental health (p<0.001). The association between the importance attached to sexual life and MH was not significant. Inclusion of ‘satisfaction with sexual life' in the relationship between ED and mental health resulted in a significant association between ‘satisfaction with sexual life' and mental health (p<0.001), whereas the association between ED and MH became insignificant (p=0.39). This indicates that satisfaction with sexual life is a potential mediator in the relationship between ED and MH. Conclusions We conclude that ED is associated with poor mental health. Satisfaction with sexual life, but not importance attached to sexual life, may play a mediating role in the association between ED and mental health. These results suggest that if men with ED can learn to be satisfied with sexual life, mental health can be preserved. This finding is useful for physicians and for men with ED when deciding on treatment (sildenafil versus counseling).