Inflation is one of the major macroeconomic problems facing Nigeria today. Over the years, the Central Bank of Nigeria (CBN) has been using monetary policy instruments in tackling inflation in the country. However, the menace of inflation has not been adequately put under control. It is therefore necessary to examine the effectiveness of monetary policy instruments in combating inflation in Nigeria: This study therefore examines the efficacy of monetary policy instruments in fighting inflationary pressure in Nigeria. Specifically, the study examines the impact of reserve requirement, liquidity ratio, treasury bill rate, monetary policy rate and money supply on inflation in Nigeria. Annual time-series data from 1981 to 2019 were used for the study. A variety of analytical techniques such as Phillips-Perron unit root test, Johansen cointegration test and error correction model was used in analyzing the data. The findings indicated that reserve requirement, liquidity ratio, monetary policy rate and Treasury bill rate have no significant influence on inflation in Nigeria. The main recommendation is that there should be a proper co-ordination of monetary and fiscal policies to reduce conflicts in the implementation of both policies.