OBJECTIVES: A comparative crossover study was conducted to assess the efficacy of brimonidine gel 0.33% (BG) vs azelaic acid gel 15% (AG) for the treatment of persistent facial erythema of rosacea using three assessments: clinician’s erythema assessment (CEA), patient self-assessment (PSA), and chromameter instrumentation.   METHODS: This was a multicenter, randomized, controlled, double-masked crossover design study. Seventy men and women with moderate to severe erythema of rosacea were included. Subjects were randomized 1:1 to either BG once daily or AG twice daily for 15 days. After a washout period, subjects were given the other treatment for 15 days. The primary efficacy endpoint was composite success defined as a 2-grade improvement in both the CEA and PSA 6 hours after application on day 15. Secondary endpoints included 2-grade improvement in CEA and PSA and changes in chromameter readings 6 hours after application on day 15.  All outcomes were in comparison to baseline (Day 0). RESULTS: Per the protocol, the results of the second period were discarded as there was significant treatment carryover from the first period. The percentage of subjects with composite success in period 1 was 14.3% and 5.7% for BG and AG, respectively. The percentage of subjects with a 2-grade improvement for CEA was 37.1% and 11.4% for BG and AG, respectively and those with a 2-grade improvement in PSA was 28.6% and 20.0% for BG and AG, respectively. Chromameter readings decreased by 9.64% and 2.38% for BG and AG, respectively. CONCLUSIONS: Improvements were larger and more pronounced with the CEA and chromameter than with the PSA suggesting that subjects may view their rosacea severity and improvements with treatment differently than either a clinician or objective instrumentation.