The purpose of this study was to evaluate inadequate hemodialysis risk in patients with body weights in the upper quartile of a sample distribution using the urea reduction ratio (URR). Using a case-control design and a simple random sample (n = 315) of hemodialysis (HD) patients, postdialysis weights were divided into quartiles based with a cut-off value at the upper quartile, which was equal to > 81 kilograms (kg). The dichotomous outcome, URR > 65% and URR < 65% constituted the classification for inadequate dialysis risk. The odds ratio (OR) was used to evaluate inadequate dialysis risk based on this outcome. A multivariate logistic regression model was used to adjust for confounding variables and validated for goodness of fit. Those in the > 81 kg group were given more dialysis session time in minutes and used higher efficiency dialyzers as indicated by the coefficient of ultrafiltration (KUf), yet were more likely to have URRs < 65% compared to other patients in the sample (p < 0.001). This finding persisted in the logistic regression model when simultaneously fitting both gender and dialysis session time. Patients weighing > 81 kg experienced an increased risk of inadequate dialysis when compared to all others (OR 4.02, 95% CI [confidence interval] 2.217-7.29). A postdialysis weight > 81 kg increased the risk of inadequate dialysis for patients in this sample. This effect was confounded by a dialysis time x weight interaction term. Also, women were found to have a lower inadequate dialysis risk compared to men after adjusting for weight classification. We, therefore, conclude that patients who weigh > 81 kg may experience inadequate dialysis despite longer, more efficient dialysis sessions. Longer dialysis sessions may benefit some patients, but the effect in larger patients may not be a uniform response.