Objective To evaluate ocular surface changes following minimal vitreoretinal surgery in postmenopausal women patients with proliferative diabetic retinopathy (PDR). Methods Sixty-one women PDR patients (61 eyes) underwent vitreous microsurgery were recruited in this prospective study, including 31 postmenopausal women (PMW group) and 30 non-postmenopausal women (non-PMW group). The contralateral eyes were considered as the control group. Corneal fluorescein (FL) staining, tear break-up time (TBUT), Schirmer I test (SIT), central corneal sensitivity and ocular surface disease index (OSDI) were estimated. All tests were carried out 1 day preoperatively and 1 day, 10 days, 1 month and 3 months postoperatively. The student’st test or Mann-WhitneyU and ANOVA for repeat measurements test were used. Results Preoperatively, TBUT of surgery and non-surgery eyes in PMW were shorter than non-PMW (t=−2.115, −2.035;P＜0.05), but higher OSDI scores were found in PMW (t=2.482, 2.208;P＜0.05). TBUT reduction rate (Z=−2.771, −1.993;P＜0.05) and OSDI rising rate (Z=2.539, 2.157;P＜0.05) of surgery eyes in PMW were higher than non-PMW 1 day and 10 days postoperatively. The lower SIT of surgery eyes in PMW were observed at 1 day and 10 days (t=−2.403, −2.029;P＜0.05) after surgery. At 10 days after surgery, FL and OSDI scores of surgery eyes in non-PMW returned to preoperative level (Z=−0.447, −0.513;P＞0.05), but in PMW, the recovery process experienced 1 month (Z=−1.500, −0.853;P＞0.05). TBUT and SIT of surgery eyes in two groups both reached preoperative level at 1 month following surgery (Z=−0.715, −1.266, −1.531, −0.522;P＞0.05). Conclusions PMW with PDR had ocular surface dysfunction, which resulted in aggravated dry eye after minimal vitreoretinal surgery.