Purpose: To report the incidence of postoperative endophthalmitis (PE) after immediate sequential bilateral cataract surgery (ISBCS) in Sweden. Design: Retrospective cohort registry study. Participants: Patient data from 1 457 172 cataract extractions, including 1 364 934 unilateral surgeries and 92 238 ISBCSs. Methods: Endophthalmitis cases reported to the Swedish National Cataract Register (NCR) during a 16-year period (2002–2017) were analyzed in comparison to all control cases with regard to patient characteristics, surgical technique, and capsule complication. Main Outcome Measure: Incidence and determinants for PE in ISBCS compared with unilateral surgeries. Results: A total of 422 cases of PE were identified in 1 457 172 cataract extractions, yielding an overall incidence of 0.029% (95% confidence interval [CI], 0.0262–0.0317). For unilateral procedures, the rate was 0.0299% (95% CI, 0.0270–0.0328) or 408 cases in 1 364 934 operations, whereas that for ISBCS was 0.0152% (95% CI, 0.0072–0.0231) or 14 incidents in 92 238 operations (P = 0.01). In a logistic regression model including all cataract procedures, nonuse of intracameral (IC) antibiotics (ABs), capsule complication, age 85 years or more, male gender, and ocular comorbidity were found to be independent risk factors for PE. All these parameters were less frequent in ISBCS. Notwithstanding, in the same multivariate analysis, ISBCS in itself was associated with a significantly lower risk for PE. At follow-up, 5 of the 14 PE cases in the ISBCS cohort had a visual acuity (VA) of 20/200 or worse. Of these, one 93-year-old ISBCS patient developed bilateral infection. Conclusions: After ISBCS in Sweden, PE occurred once in 6600 surgeries. The risk of sustaining a final VA of 20/200 or less was 1 incident in 18 000 operated eyes. When counseling potential ISBCS patients about the risk of PE, it seems reasonable to state that the reported risk in the literature is lower than that with unilateral surgery but not negligible. Precautions remain necessary.