Background: Insufficient adherence to treatment is a relevant problem. This study aims to determine the impact of health locus of control, stress coping style and level of mindfulness on medication adherence in patients with a chronic illness. Methods: The study included 768 people. The diagnostic survey involved the use of: Medication Adherence Questionnaire (MAQ), Multidimensional Health Locus of Control Scale (MHLC), The Coping Inventory for Stressful Situations (CISS), and The Mindful Attention Awareness Scale (MAAS). Results: Participants were divided into two subgroups, i.e., adherent (n = 219) and non-adherent (n = 549). We observed significant differences between the subgroups in age, BMI, sex, place of residence, education, and for all MHLC subscales, two CISS subscales and MAAS. The identified medication adherence variables were: female gender (OR = 1.55), BMI (OR = 0.95), MHLC/Internal (OR = 0.95), CISS/Emotional (OR = 1.03), MAAS (OR = 0.97). Conclusions: A strong internal health locus of control, a higher level of mindfulness and a lower level of emotional-stress coping style increase the likelihood of adherence with medication recommendations in patients with chronic diseases.