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The present work focuses on evaluating the tribological behavior of ultrahigh molecular weight polyethylene (UHMWPE) with 316L stainless steel and Ti6Al4V under dry and lubricated sliding conditions using human body fluids (synovial fluid and human serum). Eighteen trials of experiments were performed using a reciprocating sliding tribometer (pin-on-disc) at 37°C based on Taguchi's L18 (21 × 32) array. The in-vitro experimental results revealed that UHMWPE offers better tribological performance under synovial fluid lubrication conditions irrespective of the counterface material. The optimization of the response variables (coefficient-of-friction (COF) and specific wear rate (WR)) was performed using optimization techniques (Taguchi and Grey relational analysis). It was revealed that Ti6Al4V counterface material under synovial fluid lubrication and normal load of 52 N exhibits the optimal tribological performance with UHWMPE. The contribution of process parameters on the COF and WR was evaluated using analysis of variance. It was established that load is the most significant parameter, affecting COF and WR. [ABSTRACT FROM AUTHOR]