Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications globally. There are generally two types: selective (COX-2) and traditional NSAIDs (COX-1). They are primarily used for the treatment of pain. They gained attention after a study about their basic mechanisms highlighted their toxicity. Several studies have reported an association between NSAIDs and risk of myocardial infarction (MI). However, the direction of the relationship is not conclusive. Further studies are needed to ascertain the direction of this relationship and evaluate the present situation with available drugs. Due to the seriousness of cardiovascular diseases as one of the leading cause of death, continuous monitoring of the NSAIDs-MI association is needed. The purpose of this dissertation was to investigate the association between NSAIDs and MI in a younger (30-64 years) Kentucky Medicaid population with a 12 year window of data. The three specific aims were: (1) to understand the characteristics of the Kentucky Medicaid population with respect to NSAID use: (2) to evaluate the NSAID-MI relationship with a 12 year follow-up in a young heavily-burdened population for cardiovascular diseases: and (3) to investigate the MI risk of meloxicam, celecoxib and naproxen compared to no exposure. A retrospective study was conducted employing data from January 1st 2000 and December 31st 2012. The data comprised demographic, prescription and medical files. Within this cohort, a nested case control study was conducted. Cases of MI were matched to four controls on race and gender. The results suggested that exposure to COX 2 presented an increased adjusted risk for MI (1.138(0.983, 1.318)). However, this risk was significantly increased for COX-2 only users compared to COX-1 only users (1.221 (1.03, 1.485)) and 30-40 year olds (1.600 (1.082, 2.367)). Meloxicam, celecoxib and naproxen compared to no exposure showed meloxicam presented a non-significant different risk for MI (1.26 (0.98, 1.63)) and celecoxib presented a significantly increased risk for MI (1.52 (1.26, 1.82)). This study considered pattern of use in determining continuous usage by looking at both continuous and sporadic users of NSAIDs and also considered patient switching patterns between classes of NSAIDs.