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Objective To investigate quantitative changes in iris blood flow after first-eye and second-eye cataract surgeries, and their correlation with increased pain in the second eye.Methods and analysis In this prospective study, 88 eyes of 44 participants who underwent uneventful cataract surgery were followed up at enrolment, 1 day before, and 1 day, 1 week and 1 month after each eye surgery. Iris blood flow was quantified by a swept-source optical coherence tomography angiography and intraoperative pain was evaluated. Participants were divided into three groups according to time intervals between two eye surgeries: ≥1 to <2 weeks (short interval), ≥2 to ≤4 weeks (medium interval) and greater than 4 weeks (long interval).Results The second eye experienced two significant increases in iris blood flow following cataract surgery: one after the first eye and the other after its own, with the latter being significantly higher than the increase observed in the operated eye after the first surgery (p<0.05). Additionally, the second eye showed higher iris blood flow density in the short interval group compared with the long and medium at specific time points (p<0.05). The bilateral pain index difference positively correlated with second eye iris blood flow density (p<0.05) and was significantly greater in the short interval group than the long interval group (p<0.05).Conclusions Iris blood flow increased in the second-operated eye post surgery compared with the first eye, which may correlate to second-eye pain. However, due to the variability in individual pain perception, a larger sample size is needed to prospectively validate our findings to improve their generalisability.Trial registration number NCT02182921.