Background: Optical coherence tomography (OCT) quantifies changes of foveal thickness and macular volume after photocoagulation in diabetic macular edema. Macular volume evaluates the whole macula, but it may underestimate changes in foveal thickness induced by photocoagulation. We undertook this study to evaluate the concordance between macular volume and foveal thickness for identifying clinically significant changes of retinal thickness after photocoagulation for diabetic macular edema. Methods: We carried out an observational, prospective, longitudinal, analytical study. Center point thickness (CPT), central subfield mean thickness (CSMT) and macular volume were measured with OCT before photocoagulation and 3 weeks after in diabetic patients with focal macular edema (January 2006-January 2010). Concordance among variables to detect clinically significant changes (CPT >17%, CSMT >11%, macular volume >3%) was identified using the kappa test. Results: Sixty eight eyes were included; 47 eyes had nonproliferative retinopathy (69.1%). CPT increased significantly in 14.7% of the sample; CSMT in 8.8%, and macular volume in 11.8%. CPT decreased significantly in 4.4%, CSMT in 8.8%, and macular volume in 42.6%. Concordance was regular for CPT and CSMT increased (57%). Concordance was good for CPT and CSMT decreased (64%). Concordance was regular for CSMT and macular volume decreased in eyes with center involvement (43%). The remaining concordances were poor. Discussion: Two independent events happen after focal photocoagulation: involution of the original thickening and increase in CPT. In order to detect both events, evaluation of foveal thickness alone or macular volume alone is insufficient. Conclusion: Identifying the efficacy and safety of treatments for diabetic macular edema requires simultaneous measurement of CPT and macular volume.