Afatinib is a second-generation epidermal growth factor receptor (EGFR) inhibitor that has been shown to be effective against EGFR-mutated non-small cell lung cancer (NSCLC) resistant to conventional EGFR inhibitors such as gefitinib and erlotinib. Although ocular side effects of gefitinib and erlotinib have been reported, those for afatinib have yet to be definitively established. This report presents details on the first case of unilateral iridocyclitis associated with the side effects of afatinib therapy. A 75-year-old Japanese male ex-smoker with EGFR-mutated NSCLC underwent afatinib therapy for multiple metastases. At 2 weeks, bilateral conjunctivitis developed. Topical medication and a 1-week afatinib washout period resulted in the improvement of the conjunctivitis. However, 3 days after the resumption of afatinib, the patient developed unilateral granulomatous anterior uveitis in his right eye. Best-corrected visual acuity (BCVA) measurement indicated a decimal visual acuity of 0.2, while the slit-lamp findings were characterized by granulomatous inflammation, keratic precipitates, Koeppe nodules and posterior synechiae. There was no evidence suggesting other intraocular inflammatory disease or metastatic tumor. The left eye was intact. The use of topical medication including steroids and a washout of afatinib resulted in a gradual subsiding of the anterior uveitis. After resolution of the anterior uveitis, oral afatinib was resumed. BCVA of the right eye finally recovered to a decimal acuity of 1.0. Ophthalmologists should be aware of the possibility that side effects associated with afatinib could cause granulomatous anterior uveitis.