Few studies have evaluated weight change in patients who initiate medical marijuana treatment to address diagnosed health concerns. The objective of this study was to examine whether patients initiating medical marijuana use for a qualifying health condition experienced changes in health and biopsychosocial functioning over time, including weight gain or loss. Specifically, this observational, longitudinal study evaluated changes in the body mass index (BMI) of adults with co-morbid obesity (body mass index [BMI] ≥ 30 kg/m) and severe obesity (BMI ≥ 40 kg/m) who were starting medical marijuana treatment for any of the 23 qualifying medical conditions at one of three dispensaries in Pennsylvania. Height and weight measurements were collected at baseline (prior to medical marijuana use) and then 90 days (± 14 days) later. Participants included in analyses (n = 52, M = 55.0 ± 13.6 years, 59.6% female) had a mean baseline BMI of 36.2 ± 5.4 kg/m and the majority sought medical marijuana for chronic pain (73.1%). No significant change in BMI was observed from baseline to month three (p > 0.05) in the sample. Additionally, no significant change in BMI was observed in the subset of patients with severe obesity (n = 12, p > 0.05). Our findings are limited by low follow-up rates and convenience sampling methodology but may help to mitigate weight gain concerns in the context of medical marijuana use.