Objective. To determine if poor compliance with asthma treatment is independently associated with exacerbations requiring emergency room visits in adult patients seen at Kalafong Hospital, a secondary regional- and teaching hospital affiliated to the University of Pretoria. Methods. A matched case-control study was undertaken - matched on age and gender, between December 2003 and May 2005. Known asthma patients with exacerbations presenting at the hospital's emergency unit were chosen as cases. Controls were stable asthma patients recruited from the outpatient departments. A structured questionnaire was used to interview patients concerning their possible exposure to certain triggers and risk factors. Univariate and multivariate analysis with conditional logistic regression was done to determine any significant exposures. Participants were between 18 ¬65 years of age. Results. Three hundred and fifty-six patients were evaluated. Fifty cases and 100 controls were enrolled. Cases were shown to be more non-compliant than controls (OR = 2.18; 95% CI 1.09 to 4.38, p = 0.03). Missing follow-up doctor appointments for the last six months was statistically significant with an OR of 2.39 (95% CI 1.08 to 5.27) and p = 0.03. Cases had more bacterial respiratory infections than controls (OR = 5.00; 95% CI 1.57 to 15.94, p = 0.01). More controls (50%) were exposed to dust- and environmental pollution than cases (38%) (OR = 0.60; 95% CI 0.29 to 1.23, p = 0.16). There was also an interaction between non-compliance and dust- and environmental pollution. Conclusion. Non-compliance and bacterial respiratory infections were strong predictors of exacerbations in adult asthma patients at Kalafong Hospital.