We conducted a retrospective group study to evaluate the potential systemic risk factors for major postoperative complications of cataract surgery. Individuals diagnosed with (n = 2046) and without (n = 8184) serious complications after cataract surgery were matched 1:4 for age, sex, and index date obtained using Taiwan’s National Health Insurance Research Database. The outcome was defined as at least one new inpatient or outpatient diagnosis of systemic disease one year before the index date. The effect of demographic data on postoperative complications was also analyzed in the multivariable model. Data were analyzed using univariate and multivariate conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals of the risk of developing serious complications. After the entire study interval, the major postoperative complications of cataract surgery were associated with the following systemic diseases: hypertension (adjusted OR (aOR) = 2.329, p < 0.001), diabetes mellitus (aOR = 2.818, p < 0.001), hyperlipidemia (aOR = 1.702, p < 0.001), congestive heart failure (aOR = 2.891, p < 0.001), rheumatic disease (aOR = 1.965, p < 0.001), and kidney disease needing hemodialysis (aOR = 2.942, p < 0.001). Additionally, demographic data including old age, higher urbanization level, higher level of care, and more frequent inpatient department visits were associated with a higher rate of postoperative complications. In conclusion, metabolic syndrome, chronic heart failure, end-stage renal disease, rheumatic disease, older age, and frequent inpatient department visits are correlated with the development of severe postoperative complications of cataract surgery. Therefore, cataract surgery patients should be informed about a higher possibility of postoperative complications.