Previous studies have reported that 15% to 25% of patients treated for breast cancer experience long-term moderate-to-severe pain in the area of surgery, potentially lasting for several years. Few prospective studies have included all potential risk factors for the development of persistent pain after breast cancer surgery (PPBCS). The aim of this prospective cohort study was to comprehensively identify factors predicting PPBCS. Patients scheduled for primary breast cancer surgery were recruited. Assessments were conducted preoperatively, the first 3 days postoperatively, and 1 week, 6 months, and 1 year after surgery. A comprehensive validated questionnaire was used. Handling of the intercostobrachial nerve was registered by the surgeon. Factors known by the first 3 weeks after surgery were modeled in ordinal logistic regression analyses. Five hundred thirty-seven patients with baseline data were included, and 475 (88%) were available for analysis at 1 year. At 1-year follow-up, the prevalence of moderate-to-severe pain at rest was 14% and during movement was 7%. Factors associated with pain at rest were age <65 years (odds ratio [OR]: 1.8, P = 0.02), breast conserving surgery (OR: 2.0, P = 0.006), axillary lymph node dissection with preservation of the intercostobrachial nerve (OR: 3.1, P = 0.0005), moderate-to-severe preoperative pain (OR: 5.7, P = 0.0002), acute postoperative pain (OR: 2.8, P = 0.0018), and signs of neuropathic pain at 1 week (OR: 2.1, P = 0.01). Higher preoperative diastolic blood pressure was associated with reduced risk of PPBCS (OR: 0.98 per mm Hg, P = 0.01). Both patient- and treatment-related risk factors predicted PPBCS. Identifying patients at risk may facilitate targeted intervention.