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Purpose The aim of this study was to compare the accuracy and clinical outcome of closed versus open-sky approach of Muller muscle–conjunctival resection for correction of mild and moderate ptosis with good levator function and positive phenylephrine test. Patients and methods A prospective comparative nonrandomized interventional study was conducted on patients attending the Outpatient Clinic of the Ophthalmology Department in Al Azhar University Hospital (Damietta branch) during the period from April 2018 to August 2019. The study was conducted on 50 eyelids of 45 patients with mild to moderate ptosis with good levator function and positive phenylephrine test. The patients were treated with either a closed or open-sky approach of Muller muscle–conjunctival resection, with 25 eyelids being treated by each approach. A total of 40 cases had unilateral ptosis and five cases were bilateral. All cases were congenital except one case that was a Pancoast tumor causing preganglionic Horner’s syndrome. The eyelid elevation, marginal reflex distance 1, lid contour, dry eye, and symmetry between both eyelids were the main outcome measures. Results There were significant differences between the two groups regarding the postoperative marginal reflex distance 1 (3.64±0.44 mm in the open-sky approach vs. 3.18±0.53 mm in the closed approach, P=0.002). There was significantly more correction of the degree of ptosis in the open-sky approach. Undercorrection was reported in 4% of the cases in the open-sky approach versus 28% in the closed approach, whereas temporal flare was reported in only 4% of the cases in the open-sky approach (P=0.0047). There was a significant reduction in the postoperative tear film in the patients treated with the closed approach in comparison with those treated with open-sky approach (P=0.007). Conclusion The open-sky approach offered advantages over the closed approach, including the opportunity for adjustment of the lid height and reducing the risk of dry eye.