Background: Gravity confounds arm movement ability in post-stroke hemiparesis. Reducing its influence allows effective practice leading to recovery. Yet, there is a scarcity of wearable devices suitable for personalized use across diverse therapeutic activities in the clinic. Objective: In this study, we investigated the safety, feasibility, and efficacy of anti-gravity therapy using the ExoNET device in post-stroke participants. Methods: Twenty chronic stroke survivors underwent six, 45-minute occupational therapy sessions while wearing the ExoNET, randomized into either the treatment (ExoNET tuned to gravity-support) or control group (ExoNET tuned to slack condition). Clinical outcomes were evaluated by a blinded-rater at baseline, post, and six-week follow-up sessions. Kinetic, kinematic, and patient experience outcomes were also assessed. Results: Mixed-effect models showed a significant improvement in Box and Blocks scores in the post-intervention session for the treatment group (effect size: 2.1, p = .04). No significant effects were found between the treatment and control groups for ARAT scores and other clinical metrics. Direct kinetic effects revealed a significant reduction in muscle activity during free exploration with an effect size of (-7.12%, p< 005). There were no significant longitudinal kinetic or kinematic trends. Subject feedback suggested a generally positive perception of the anti-gravity therapy. Conclusions: Anti-gravity therapy with the ExoNET is a safe and feasible treatment for post-stroke rehabilitation. The device provided anti-gravity forces, did not encumber range of motion, and clinical metrics of anti-gravity therapy demonstrated improvements in gross manual dexterity. Further research is required to explore potential benefits in broader clinical metrics.