Antimalarials are very useful drugs in the treatment of various rheumatic diseases. One of their main side effects is ocular toxicity, specifically retinopathy. Our objective was to identify risk factors associated with chloroquine retinopathy. A single, trained evaluator reviewed patient records with rheumatic diseases. They were taking chloroquine and identified by the ophthalmology department as having retinopathy during their routine eye evaluation. These cases were classified according to clinical evaluation, visual fields and fluorangiographic study. Up to four controls were selected for each case, matched by age, gender, diagnosis and similar time on chloroquine. In all, 34 variables were studied, among these: weight, age, disease duration, keratopathy, total cumulative dose (TCD), mean daily dose (MDD), lean body weight adjusted daily dose (LBWDD) and laboratory tests. Descriptive and inferential statistics comparing cases and controls in all patients and subgroup analysis were carried out. Significance was set at the 0.05 level. Odds ratio and 95% confidence intervals were calculated. Sixteen cases of chloroquine retinopathy were identified, eight patients with rheumatoid arthritis (RA), seven with systemic lupus erythematosus (SLE) and one with dermatomyositis. All were female. Mean age was 47.3 +/- 12.2 years; weight 59.5 +/- 10.7 kg; disease duration 12.8 +/- 6.0 years; time on chloroquine 54.1 +/- 27.8 (min-max: 30-197) months. There was a significant difference in the following variables in all patients: MDD 212.3 +/- 52.6 versus 170 +/- 51.3, p = 0.009; and LBWDD 5 +/- 1 versus 4.2 +/- 1.5, p = 0.03, for cases and controls, respectively. In subgroup analysis the MDD remained significantly different (235.5 +/- 45.8 versus 169.7 +/- 46.1, p = 0.004) only in RA, whereas LBWDD was different both in SLE and RA. Keratopathy increased the risk for retinopathy: OR, 95% CI: 5, 1.4-17.6, p = 0.01. In conclusion, in accordance with previous studies, the MDD, LBWDD and keratopathy were risk factors associated with chloroquine retinopathy. Periodic ophthalmologic evaluations are mandatory.