Low-income minorities often face system-based and personal barriers to screening colonoscopy (SC). Culturally targeted patient navigation (CTPN) programs employing professional navigators (Pro-PNs) or community-based peer navigators (Peer-PNs) can help overcome barriers but are not widely implemented. In East Harlem, NY, USA, where approximately half the residents participate in SC, 315 African American patients referred for SC at a primary care clinic with a Direct Endoscopic Referral System were recruited between May 2008 and May 2010. After medical clearance, 240 were randomized to receive CTPN delivered by a Pro-PN (n = 106) or Peer-PN (n = 134). Successful navigation was measured by SC adherence rate, patient satisfaction and navigator trust. Study enrollment was 91.4% with no significant differences in SC adherence rates between Pro-PN (80.0%) and Peer-PN (71.3%) (P = 0.178). Participants in both groups reported high levels of satisfaction and trust. These findings suggest that CTPN Pro-PN and Peer-PN programs are effective in this urban primary care setting. We detail how we recruited and trained navigators, how CTPN was implemented and provide a preliminary answer to our questions of the study aims: can peer navigators be as effective as professionals and what is the potential impact of patient navigation on screening adherence?