We investigated the incidence of prostaglandin-associated periorbitopathy (PAP) in subjects with glaucoma treated with latanoprost ophthalmic solution.One eye and the forehead in 22 subjects were evaluated. All patients had used latanoprost for more than 1 year (range, 12 to 45 months; mean, 26.0 months) and were prostaglandin F2α analogue treatment-naïve. Digital photographs of the subjects obtained before latanoprost therapy and at the last examination were compared retrospectively. Four signs of PAP (deepening of the upper eyelid sulcus (DUES), upper eyelid ptosis, flattening of the lower eyelid bags, and inferior scleral show) and supplemental side effects around the eyelids (eyelash growth, poliosis, and eyelid pigmentation) were judged to be negative or positive by three independent observers. If the observers unanimously rated a sign as positive, the result was defined as positive.Twelve subjects (54.5%) had no apparent signs. Three subjects were judged to have DUES (13.6%), and two subjects each were judged to have flattening of the lower eyelid bags and eyelid pigmentation (9.0%). The other signs were judged as positive in only one subject each, respectively (4.5%). A univariate logistic regression analysis showed no significant associations between any of the signs and age, sex, or the duration of therapy.Latanoprost induced DUES, upper eyelid ptosis, flattening of the lower eyelid bags, inferior scleral show, and supplemental side effects around the eyelids; however, the rates of such occurrence might be relatively low.