This study presents deterministic and probabilistic human health risk assessment using Monte Carlo simulations on exposure to an Indian river, Kaveri, which has been contaminated by non-steroidal anti-inflammatory drugs (NSAIDs). The NSAIDs of concern are naproxen, ibuprofen, aspirin, ketoprofen, and diclofenac. We have considered three exposure scenarios (water ingestion, dermal exposure, and fish ingestion) for four different age groups (0–5, 6–10, 11–18, and 19–70 years). Deterministic risk assessment revealed teenagers to be the most sensitive receptors and water ingestion to be the most crucial pathway contributing to maximum health risk (79 to 86%). Based on the results of Monte Carlo simulations, it was found that the probability of exceeding the deterministic mean risks ranged from 17 to 39% for different exposure routes. High end risk estimates such as 95th percentiles and maximum values of HQ for the entire population did not exceed the USEPA allowable risk. This implies that the NSAIDs at the detected concentrations in the Kaveri river may not pose adverse health effects even in the worst-case scenario. Among the five NSAIDs, diclofenac was found to be the major contributor for health risk. Moreover, the concentration of diclofenac was just one order less than the estimated site-specific threshold concentrations. From sensitivity analysis, the most and the least impactful parameters were found to be water ingestion rate and fish ingestion rate respectively. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.