Background: A study by the US Army suggests medications can last longer than their labeled expiration date. Meanwhile, use of expired drugs has become common in Nigeria. There is need to evaluate how efficacious and safe this practice is. Method: Expired non-steroidal anti-inflammatory drugs were tested for efficacy using the fresh egg albumin-induced mice paw edema method. Some blood parameters were also monitored. Findings: Expired ibuprofen and diclofenac potassium recorded no activity at the 1st hour. However, there were activities in all 3 NSAIDs at the 2nd, 3rd and 4th hours. The liver enzymes studies for expired ibuprofen and diclofenac show that their ratio of AST:ALT (3.65) is lower than the value of negative control while piroxicam (14.05) is higher. The ratio of ALT:ALP for the 3 drugs was generally low and within the range 0.31 and 0.5. Even though piroxicam has a higher AST:ALT value than the control, there is no statistical significance when the individual values of AST and ALT is compared with the control. The blood urea show a rise in the values for ibuprofen and diclofenac when each of them is compared with the control, while piroxicam caused a drop in value. There was a general drop in blood bilirubin level below the control. However, bilirubin values for ibuprofen were significant statistically. Conclusion: Our study compared the control with either the expired or unexpired equivalents. The outcome of both comparisons seems different, suggesting that the activities of the expired and unexpired samples are not the same. Climate, culture and environment may be responsible for the observed discrepancies.