ABSTRACT Purpose To identify and evaluate the risk factors for ptosis repair failure. Methods Retrospective, case-controlled study evaluating adult patients with ptosis who underwent ptosis surgery by external levator advancement/resection (ELR) or Müller muscle conjunctival resection (MMCR) with at least 3 months postoperative follow-up. Regression analyses were performed of ptosis repair outcomes comparing preoperative and perioperative risk factors for failure. Results A total of 240 patients (404 eyelids) met the inclusion criteria for the study. Surgical outcomes were measured categorically by success rate and measured quantitively over time using Kaplan–Meier survival analysis. Success was categorically achieved in 101/112 (90%) eyelids after MMCR and 231/292 (79%) eyelids after ELR (p = .0088). Success as measured over 5 years of follow-up was significantly better in eyelids following MMCR compared to ELR (p = .0469). In terms of surgical failure, the following variables were found to be predictive in order of decreasing risk: chronic topical prostaglandin use, chronic topical corticosteroid use, surgical approach, lower preoperative margin reflex distance 1, prior intraocular surgery, age, lower preoperative levator function, concomitant blepharoplasty, presence of a glaucoma filtering bleb, and female gender. Conclusions Ptosis repair surgery is a complex and challenging procedure. This study provides the largest comparative analysis of ELR versus MMCR to date with findings suggesting MMCR to be more a successful surgery than ELR. Topical prostaglandin analogue use appears to be the highest known risk factor for MMCR and ELR ptosis repair failure.