Background: The selective removal or inhibition of pathogenic microbes with locally delivered antimicrobials when combined with scaling and root planing is often an effective approach for the managment of chronic periodontitis. Aim: To compare the clinical efficacy of tetracycline fibers and a xanthan based chlorhexidine gel in the treatment of chronic periodontitis. Methods and materials: Thirty systemically healthy patients in the age group of 30-50 years suffering from generalized chronic moderate periodontitis were selected. For each subject, two experimental sites were chosen that had probing depth >5mm and were located in symmetric quadrants and the sites were randomized at split mouth level with one receiving tetracycline fibers and the other chlorhexidine gel. Plaque score, bleeding score, probing pocket depth and relative attachment level gain was recorded on day 0 and at the end of 3 months. Results and conclusion: In both groups, there was statistically highly significant reduction in all the clinical parameters i.e. plaque score, bleeding score and probing pocket depth and relative attachment level gain was seen at different time intervals. Local delivery of tetracycline and chlorhexidine is a safe, easy and efficacious method along with scaling and root planing in the treatment of chronic periodontitis. Inter-comparison of both local drug delivery agents with respect to clinical changes shows that tetracycline fibers are better than chlorhexidine gel for treatment of chronic periodontitis. Nevertheless, long term studies with more samples are suggested to further evaluate and compare the efficacy of both materials.