© Avantika Naidu, David Brown, Elliot Roth. Background: Body weight support treadmill training protocols in conjunction with other modalities are commonly used to improve poststroke balance and walking function. However, typical body weight support paradigms tend to use consistently stable balance conditions, often with handrail support and or manual assistance. Objective: In this paper, we describe our study protocol, which involved 2 unique body weight support treadmill training paradigms of similar training intensity that integrated dynamic balance challenges to help improve ambulatory function post stroke. The first paradigm emphasized walking without any handrails or manual assistance, that is, hands-free walking, and served as the control group, whereas the second paradigm incorporated practicing 9 essential challenging mobility skills, akin to environmental barriers encountered during community ambulation along with hands-free walking (ie hands-free + challenge walking). Methods: We recruited individuals with chronic poststroke hemiparesis and randomized them to either group. Participants trained for 6 weeks on a self-driven, robotic treadmill interface that provided body weight support and a safe gait-training environment. We assessed participants at pre-, mid- and post 6 weeks of intervention-training, with a 6-month follow-up. We hypothesized greater walking improvements in the hands-free + challenge walking group following training because of increased practice opportunity of essential mobility skills along with hands-free walking. Results: We assessed 77 individuals with chronic hemiparesis, and enrolled and randomized 30 individuals poststroke for our study (hands-free group=19 and hands-free + challenge walking group=20) from June 2012 to January 2015. Data collection along with 6-month follow-up continued until January 2016. Our primary outcome measure is change in comfortable walking speed from pre to post intervention for each group. We will also assess feasibility, adherence, postintervention efficacy, and changes in various exploratory secondary outcome measures. Additionally, we will also assess participant responses to a study survey, conducted at the end of training week, to gauge each group's training experiences. Conclusions: Our treadmill training paradigms, and study protocol represent advances in standardized approaches to selecting body weight support levels without the necessity for using handrails or manual assistance, while progressively providing dynamic challenges for improving poststroke ambulatory function during rehabilitation.