The rate of return earned by a Pharmaceutical firm is affected by numerous factors. Thesefactors include elements internal to each Pharmaceutical firm and several importantexternal forces shaping profitability. While the internal forces can be easily manipulated and controlled by firm‘s management. It was on this note that this study examined the determinants of profitability of listed pharmaceutical firms in Nigeria. To achieve the stated objectives, secondary data was collected over a period of 7 years (2011-2016) from the annual reports and accounts of 7listed Pharmaceutical firms using censor sampling technique. The data gathered went through various robustness tests using STATA 10 where panel regression was adopted as a tool of data analysis. The result revealed that internal factors of liquidity, leverage and tangibility have significant effects on profitability,while firm size and age have no significant effect on the profitability of Pharmaceutical firms for the period under study. The study concluded that the major internal determinants of profitability of listed pharmaceutical firms are: liquidity, leverage and asset tangibility. Based on these findings, the study recommends that board of directors should maintain the level of those internal factors that are significant in order to reduce information asymmetry and subsequently add value to the firms.