The aim of this study was to examine the joint role of demographic, clinical, and psychological variables as predictors of acute postsurgical pain in women undergoing hysterectomy due to benign disorders. A consecutive sample of 203 women was assessed 24hours before (T1) and 48hours after (T2) surgery. Baseline pain and predictors were assessed at T1 and postsurgical pain and analgesic consumption at T2. Several factors distinguished women who had no or mild pain after surgery from those who had moderate to severe pain, with the latter being younger, having more presurgical pain, and showing a less favorable psychological profile. Younger age (odds ratio [OR]=0.90, P<.001), presurgical pain (OR=2.50, P <.05), pain due to other causes (OR=4.39, P=.001), and pain catastrophizing (OR=3.37, P=.001) emerged as the main predictors of pain severity at T2 in multivariate logistic regression. This was confirmed in hierarchical linear regression (β=−0.187, P<.05; β=0.146, P<.05; β=0.136, P<.05; β=0.245, P<.01, respectively). Presurgical anxiety also predicted pain intensity at T2. Findings revealed an integrative heuristic model that accounts for the joint influence of demographic, clinical, and psychological factors on postsurgical pain intensity and severity. In further mediation analysis, pain catastrophizing emerged as a full mediator between presurgical anxiety and postsurgical pain intensity. The potential clinical implications for understanding, evaluating, and intervening in postsurgical pain are discussed.