There have been limited studies evaluating specifically the incidence of wound dehiscence following isolated upper blepharoplasty. This is a large-scale upper blepharoplasty review to evaluate the rate of wound dehiscence, to assess risk factors, and to analyze management outcomes. A retrospective review was performed of all patients who underwent upper blepharoplasty at a single surgery center. All incisions were closed using either 6-0 fast-absorbing plain gut or polypropylene suture in a running fashion, with an additional interrupted suture near the lateral wound edge. Incidence of wound dehiscence was determined and further assessed by patient age (≤67 or >67 years), gender, preexisting medical conditions, smoking history, and suture type. A total of 1,190 patients (2,376 eyelids) met inclusion criteria. In total, there were 34 instances (1.4%) of wound dehiscence in 32 patients at an average 9 days (range, 0-30 days) following surgery. Evaluation of wound dehiscence rates by demographic factors revealed male gender to be a significant predictor of wound dehiscence (p = 0.0062). Age, hypertension, heart disease, and diabetes were not predictors of wound dehiscence. Lifetime smoking history increased risk for wound dehiscence (p < 0.0001). Use of fast-absorbing plain gut suture was also significantly associated with dehiscence, when compared with polypropylene (p = 0.0025). Multivariate analysis revealed male gender and fast-absorbing plain gut suture to be independent risk factors for wound dehiscence. Seventeen eyelids with wound separation were observed for second-intention healing, 1 underwent delayed scar revision. Fourteen eyelids were repaired primarily using suture and 3 with cyanoacrylate surgical skin adhesive. All patients reported satisfaction with their final outcome, and objective final healing was deemed satisfactory. Wound dehiscence following isolated upper blepharoplasty is rare and associated with male gender and fast-absorbing plain gut suture. Patients with wound separation may be successfully managed with individualized care.