Karachi is the only mega city in the world with persistent poliovirus transmission. We determined routine childhood immunization rates in Karachi and identified predictors of vaccine completion. A population-based cross-sectional survey was conducted in Karachi between August and September 2008. Data on demographics, socioeconomic, and DTP3 vaccination status in children 12 to 23 months old were collected. Logistic regression was used to identify predictors of vaccination completion. Overall, 1401 participants were approached; 1391 consented to participate. Of these, 1038 (75%) were completely vaccinated. Punjabi families had the highest DTP3 coverage (82%), followed by Urdu-speaking families (79%). Pashtun (67%) and Bengali (48%) families had the lowest vaccine coverage. Children of mothers with ≥12 years of schooling (OR = 25.4; 95% CI = 5.7-113.1) were most likely to be vaccinated. A quarter of study participants were unvaccinated. Targeted strategies for boosting DTP3 rates in communities with low immunization coverage are essential for polio eradication in Karachi.