The success of a clinical trial is largely dependent on the clinical sites that enroll the subjects, complete the follow-up visits, and collect the data. Many clinical trials are conducted using multiple site locations. Choosing such sites to participate in a clinical trial is an important aspect of study implementation. In the past, multi-center clinical trials were conducted mainly using university-based centers. In the last few decades, private practice, or community-based, centers have been included more often in clinical trial research. As more community-based centers participate in clinical trials, it is crucial to examine how these centers might differ from university-based centers. The purpose of this project was to compare community-based and university-based centers participating in a multi-center randomized trial evaluating treatments for diabetic macular edema. Aspects of recruitment, retention, protocol adherence, data collection, and observance of study required procedures were compared. Data from 102 participating centers were examined with 40 centers categorized as university-based and 62 centers categorized as community-based. Various measures of trial performance were compared using Wilcoxon rank-sum test, repeated measures logistic regression, and repeated measures analysis of variance (ANOVA), depending on the variable being compared. Characteristics of the centers and baseline subject characteristics were compared to evaluate for possible confounding. We found that university-based and community-based centers performed similarly in almost all performance aspects compared. Notable differences included community-based centers becoming certified for participation in the study 90 days sooner on average and university-based centers having half the percentage of ungradable fundus photographs. Overall, it is recommended that community-based centers be included more often in multi-center clinical trials.