Sex differences in clinical and experimental pain responses have been widely reported; however, few studies have examined sex differences in outcomes from interventional pain treatment and the predictors thereof. The aims of this study were to examine sex differences in (1) the acute pain produced by epidural steroid injections (ESIs), (2) clinical improvements in pain and pain-related psychological distress and disability after ESIs, and (3) predictors of the clinical response to ESIs. A total of 57 patients (37 menopausal women and 20 men), seen in the pain clinic of a regional medical center for ESI therapy, participated. Patients rated the painfulness of the ESI procedure itself. Also, clinical pain, depression, and disability were assessed before treatment and at 2 weeks and 2 months after the ESIs. Participants also were queried about their expectations of successful pain relief, coping strategies, and pain-related anxiety, which were examined as predictors of treatment outcome. Men reported significantly greater pain intensity and unpleasantness than women for the first injection only. All groups showed significant reductions in clinical pain, depression, and disability at 2 weeks compared to baseline, but minimal change occurred between 2 weeks and 2 months past baseline. No sex differences in the magnitude of treatment response emerged; however, specific dimensions of pain coping were associated with treatment responses in a sex-dependent manner. These findings suggest that the determinants of ESI pain and treatment outcome might differ across sex. CONCLUSIONS Sex-related influences on pain responses have been widely reported, but few studies have explored sex-dependent predictors of treatment response. These findings indicate that pain coping was differentially associated with outcomes after ESI in women versus men.