BACKGROUND: The present study describes an assessment of a large-scale intervention, "Avahan", using an evaluation framework that assesses the program coverage, changes in injection patterns, condom use, and STI and HIV prevalence among People Who Inject Drugs (PWID) in two states of India - Manipur and Nagaland. METHODS: Program monitoring data and results from two rounds of a cross sectional biological and behavioural surveys in 2006 (Round 1) and 2009 (Round 2) were used. The sample included 839 and 860 PWIDs from Manipur and 821 and 829 PWIDs from Nagaland in Round 1 and Round 2 respectively for current analysis. Bivariate and multivariate analyses were done to measure the changes in behavioural and biological outcomes between the two rounds and to examine the association between programme exposure and behavioural outcomes. RESULTS: In Manipur, about 77% of the PWIDs were contacted by the peer educators/outreach workers every month and about 18% of the PWIDs visited the clinic every month by March 2010. In Nagaland, however, the proportion of PWIDs visiting the clinic monthly remained low (11% in March 2010). PWIDs in both states were more likely to report 'consistent safe injection practice in the last six months' in Round 2 compared to Round 1 (Manipur: adjusted odds ratio (aOR): 1.88, 95% confidence intervals (CI): 1.46-2.43; Nagaland: aOR: 2.35, 95% CI: 1.86-2.80) PWIDs were also more likely to report consistent condom use with regular partners in Round 2. The prevalence of Hepatitis B virus (HBV) increased in Round 2 in Manipur (11% vs 6%, p<0.001) and Nagaland (8% vs 6%, p=0.05). The prevalence of Hepatitis C virus (HCV) was high and did not change, either in Manipur (67.3% vs 69.9%, p=0.42) and Nagaland (14.7% vs 15.1%, p=0.82). Similarly, the prevalence of HIV did not change significantly between the two Rounds either in Manipur (27.8% in Round 1 vs 29.2% in Round 2, p=0.59) or in Nagaland (1.2% in Round 1 and 1.6% in Round 2 of the IBBA, p=0.82). CONCLUSION: Improvements in safe injection practices and consistent condom use with regular partners suggest effectiveness of prevention efforts. However, increase in HBV prevalence and non-decline in HCV and HIV prevalence in both the states also underscore the need to continue and intensify targeted interventions (such as Hepatitis B vaccination, needle exchange programmes, condom distribution) for long term risk reduction among PWID population.