OBJECTIVES: The goal of this study was to compare the performance of treatment of painful diabetic peripheral neuropathy (PDPN) — duloxetine, pregabalin, gabapentin, amitriptyline, and their combinations based upon pain reduction reported in clinical trials, and inform a revised treatment algorithm. METHODS: Published studies of PDPN treatment through May 2012 were identified from MEDLINE(PubMed) database and extended manual search was conducted based on citations from identified studies. Inclusion criteria was restricted to randomized controlled trials lasting at least 5 weeks and at most 12 weeks and studies examining 30% pain reduction or equivalent. Direct and indirect pairwise odds ratios (OR) were obtained. The study used Bayesian Analysis Using Gibbs Sampling in Windows (WinBUGS) version 1.4.3. and Monte Carlo Simulations to conduct a multiple treatment comparison. Results are reported in OR with 95% credible intervals (CI) and the median of ranking. RESULTS: There were a total of 10 studies with 23 treatment arms, representing 2,885 subjects enrolled, that were included in the analysis. The results from fix effects model indicated that duloxetine, pregabalin, gabapentin, and co-administration of duloxetine and gabapentin were significantly better than amitriptyline (OR= 3.22[95%CI, 1.54-7.17], OR = 2.53[95%CI, 1.11-5.94], OR =  4.00[95%CI, 1.33-11.69], OR  =  2.86[95%CI, 1.09-7.48], respectively). The results from random effects model suggested that only duloxetine and pregabalin were significantly better than placebo (OR = 2.61[95%CI, 1.37-4.95] and OR = 1.97[95%CI, 1.01-3.62], respectively). There was no significant difference between amitriptyline and placebo in either fixed or random effects models. With regard to the median ranking, gabapentin was ranked first, followed by duloxetine, co-administration of duloxetine and gabapentin, pregabalin, placebo, and amitriptyline from the fix effects model. CONCLUSIONS: Treatment of PDPN with amitriptyline does not appear to be significantly different from placebo. Duloxetine and pregabalin appear to be better than both amitriptyline and placebo.