The main aim of this systematic review and meta-analysis was to evaluate the safety and efficacy profile of immediate sequential bilateral cataract surgery (ISBCS) compared with delayed sequential bilateral cataract surgery (DSBCS). MEDLINE Ovid, EMBASE, and CENTRAL databases were searched. Outcome measures were postoperative visual acuity, postoperative spherical equivalent (refractive outcome), endophthalmitis, corneal edema, pseudophakic macular edema, and posterior capsule rupture (PCR). 13 articles met criteria for final inclusion. A total of 11 068 622 participants (18 802 043 eyes) were included. No statistically significant differences between ISBCS and DSBCS were identified in all the postoperative outcomes evaluated. However, a higher risk for PCR was identified in the ISBCS group from the pooled analysis of nonrandomized studies (risk ratio, 1.34, 95% CI, 1.08-1.67, P = .0081). In our view, the ISBCS approach has an acceptable safety-efficacy profile, comparable with DSBCS. Future investigations are warranted, with a focus on the analysis of risk factors for surgical complications, patient-reported outcome-measures, and cost effectiveness.