Introduction: Asthma is a respiratory disease that impacts mainly on non-controlled patients due to a higher risk of exacerbations. This risk is increased by patients' lack of adherence and the complexity of therapeutic regimens. This study reviews the relationship between adherence and therapeutic complexity in a group of difficult-to-control asthmatic patients. Method: It was done a prospective study which included non-controlled asthmatic patients who were being looked after at Clinica Aire in the San Juan de Dios Hospital, part of the Caja Costa rricense de Seguro Social, in Costa Rica. Complexity was determined using the Medication Regimen Complexity Index (MRCI) whereas adherence was measured using the Morisky-Green-Levine test. For the statistical analysis, descriptive statistical methods were used and the relationship between the variables was probed using Student's T tests and the Pearson's index. Results: A total of 22 patients were included in this study. They were mainly women with an average age of 50.5 years (SD 15.3), who used an average of 4.2 (SD 1.2) medications, with only 36.4% (n = 8) reporting adherence to treatment at the beginning of the study. The most widely used treatment strategy was the combination of inhaled corticosteroid, long-acting beta-agonist, and a leukotriene inhibitor (45.5%, n = 10). The average value of the MRCI was 20 (SD: 5.57), affected mainly by the diversity of pharmaceutical forms and frequency of administration. A non-statistically significant trend of greater adherence was observed as complexity increased (Pearson index 0.338). Conclusions: The high complexity therapeutic regimens observed in this study were associated with low adherence to treatment. This suggests that non-controlled asthmatic patients are critical population to be included in programs that promote medication adherence.